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Background: Multiwave locked system (MLS) laser therapy utilizes the synchronized emission of an 808 nm continuous laser and a 905 nm pulsed laser. It is postulated that MLS enables greater penetration and therapeutic benefit than single-wavelength low-level laser therapy (LLLT)., Objective: The aim of this research was to evaluate the efficacies of MLS laser therapy and the 830 nm laser in the treatment of patients with chronic neck pain (CNP)., Materials and Methods: Seventy-five patients with CNP (mean age 46.28 ± 5.89, weight 83.78 ± 5.65 kg, height 1.72 ± 4.96 m, and duration of illness of 5.98 ± 1.44 months). They were randomized into three groups. Group I received MLS laser therapy and exercises, Group II received LLLT and exercises, and Group III received placebo laser therapy plus exercises (PL + EX). Neck pain levels and neck function were measured using the visual analogue scale (VAS) and neck disability index (NDI), respectively., Results: Both VAS and NDI were significantly reduced post-treatment for all treatment groups. After 6 weeks of treatment, MLS plus exercise showed a significantly greater decrease in pain and disability scores {Δ VAS (6.68) and Δ NDI (39.84)} compared to both LLLT plus exercise group {Δ VAS (5.72) and Δ NDI (37.88)} and PL + EX {Δ VAS (4.84) and Δ NDI (36.68)}., Conclusions: MLS laser therapy in conjunction with exercises decreased pain and increased functional activity following 6 months of therapy. MLS laser therapy in combination with exercises is a more effective therapy for CNP compared to exercise plus LLLT or exercise alone.

Background: In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective., Patients and Methods: A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks., Results: The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded., Conclusion: Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.

The present randomized controlled split mouth clinical study aimed to investigate the efficacy of Er,Cr:YSGG laser irradiation on pain reduction and healing rate of recurrent aphthous stomatitis. 40 patients with RAS were recruited for this study and RAS ulcerations of each patient were randomly assigned to the control or test group. In the test group, Er,Cr:YSGG laser with non-contact mode was used to irradiate RAS lesions. In the placebo group, RAS lesions were irradiated with the same device without laser emission. Pain was evaluated with visual analog scale (VAS) while a clinician graded healing of RAS (HRAS). In the placebo group at immediate; scores of VAS presented no statistically significance; in the test group, laser application showed significant pain reducing, at 1st day control. In the test group, a significantly healing effect at 1st day control was observed and this effect was maintained throughout the study. In the placebo group, scores of HRAS were statistically significant at controls on 3, 7, 10days. Statistically significant difference between the scores of VAS and HRAS was found for all control days except day 10 according to the intergroup comparisons. Based on these findings, Er,Cr:YSGG laser application at 0.25W without water may be appropriate to reduce pain and also accelerate the healing of RAS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Low-dose external beam radiotherapy (ED-EBRT) is frequently used in the therapy of refractory greater trochanteric pain syndrome (GTPS). As studies reporting treatment results are scarce, we retrospectively analyzed our own patient collectives., Patients and Methods: In all, 60 patients (74 hips) received LD-EBRT (6 × 0.5 Gy in 29 hips, 6 × 1 Gy in 45). The endpoint was the patient's reported subjective response to treatment. The influence of different patient and treatment characteristics on treatment outcome was investigated., Results: At the end of LD-EBRT, 69% reported partial remission, 4% complete remission, no change 28%. A total of 3 months later (n = 52 hips), the results were 37, 33, and 30% and 18 months after LD-EBRT (n = 47) 21, 51, and 28%. In univariate analysis "inclusion of the total femoral head into the PTV" and "night pain before LD-EBRT" were correlated with symptom remission at the end of LD-EBRT, while "initial increase in pain during LD-EBRT" was significantly associated with treatment failure. In multivariable modeling "initial increase in pain" was identified as a risk factor for treatment failure (p = 0.007; odds ratio [OR] 0.209; 95% confidence interval [CI] 0.048-0.957), while "night pain" was an independent factor for remission (p = 0.038; OR 3.484; 95% CI 1.004-12.6). Three months after LD-EBRT "night pain" and "inclusion of the complete femoral neck circumference into the PTV" were predictive for remission., Conclusion: LD-EBRT represents a useful treatment option for patients suffering from GTPS. Three months after therapy two-thirds of the patients reported a partial or complete symptom remission. Especially patients who suffered from nocturnal pain seemed to benefit. Treatment appeared to be more effective when the entire circumference of the femoral neck was encompassed.

Objective . PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF) combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN). We also discussed the correlation of the measurements. Method . Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group, n = 20) or pharmacological therapy (control group, n = 20) at postoperative 48 hours. The efficacy measure was pain degree (PD) that was assessed by PainVision and visual analog scale (VAS), short form Mcgill pain questionnaire (SF-Mcgill), and numeric rate scale sleep interference score (NRSSIS). Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined. Results . The PD for persistent pain (PP) and breakthrough pain (BTP) at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP, P < 0.01; PD-BTP, P < 0.01). PD and VAS were highly correlated for both persistent pain ( r = 0.453, ρ = 0.008) and breakthrough pain ( r = 0.64, ρ = 0.001). Conclusion . PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Purpose: To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN)., Methods and Materials: A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure. Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses., Results: Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa., Conclusions: Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: To evaluate the long-term efficacy of pain reduction by two dose-fractionation schedules for radiotherapy of painful shoulder syndrome., Patients and Methods: Between February 2006 and February 2010, 312 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS)., Results: Median follow-up was 35 months (range 11-57). The overall early, delayed and long-term response rates for all patients were 83, 85 and 82 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.16); 38.2 ± 36.1 and 34.0 ± 24.5 (p = 0.19); 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.04) and 27.9 ± 25.8 and 32.1 ± 26.9 (p = 0.25), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.31); 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.10); 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.05) and 4.0 ± 3.9 and 5.3 ± 4.4 (p = 0.05), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28)., Conclusion: Radiotherapy is an effective treatment for the management of benign painful shoulder syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.

Background and Purpose: To evaluate the long-term efficacy of pain reduction by two dose fractionation schedules used for low-dose radiotherapy of painful elbow syndrome., Patients and Methods: Between February 2006 and February 2010, 199 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS)., Results: Median follow-up was 35 months (range 9-57 months). The overall early, delayed and long-term response rates for all patients were 80, 90 and 94 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 59.6 ± 20.2 and 55.7 ± 18.0 (p = 0.46); 32.1 ± 24.5 and 34.4 ± 22.5 (p = 0.26); 27.0 ± 27.7 and 23.5 ± 21.6 (p = 0.82) and 10.7 ± 15.0 and 21.5 ± 26.9 (p = 0.12), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 8.7 ± 2.9 and 8.1 ± 3.1 (p = 0.21); 4.5 ± 3.2 and 5.0 ± 3.4 (p = 0.51); 3.9 ± 3.6 and 2.8 ± 2.8 (p = 0.19) and 1.5 ± 2.3 and 2.4 ± 3.5 (p = 0.27), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28)., Conclusion: Low-dose radiotherapy is an effective treatment for the management of benign painful elbow syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.

Aim: Our aim was to evaluate retrospectively the role of the radiotherapy in the multi-disciplinary management of pain due to bone metastases., Patients and Methods: A total of 305 patients received radiotherapy with or without bisphosphonate and antalgic drugs. Tolerability and efficacy were evaluated using a Numerical Rating Scale, Pain Intensity Difference evaluation scale related to administration of the drug, a 5-point verbal scale of the patients' general impression., Results: We found differences in some patient subgroups: pain reduction was significantly more evident in patients treated with a single-fraction radiotherapy scheme. Overall, 68% of patients experienced an improvement in pain control using concomitant drugs during radiotherapy., Conclusion: Our study underlines the role of radiotherapy in the management of metastatic bone pain. The use of rapid-onset opioids to prevent predictable pain is a crucial step in managing radiotherapy. An interdisciplinary approach is recommended.

The aim of this study was to investigate the analgesic and anti-inflammatory activity of low-level laser therapy (LLLT) on the nociceptive behavioral as well as histomorphological aspects induced by injection of formalin and carrageenan into the rat temporomandibular joint. The 2.5% formalin injection (FRG group) induced behavioral responses characterized by rubbing the orofacial region and flinching the head quickly, which were quantified for 45 min. The pretreatment with systemic administration of diclofenac sodium-DFN group (10 mg/kg i.p.) as well as the irradiation with LLLT infrared (LST group, 780 nm, 70 mW, 30 s, 2.1 J, 52.5 J/cm(2), GaAlAs) significantly reduced the formalin-induced nociceptive responses. The 1% carrageenan injection (CRG group) induced inflammatory responses over the time-course of the study (24 h, and 3 and 7 days) characterized by the presence of intense inflammatory infiltrate rich in neutrophils, scanty areas of liquefactive necrosis and intense interstitial edema, extensive hemorrhagic areas, and enlargement of the joint space on the region. The DFN and LST groups showed an intensity of inflammatory response that was significantly lower than in CRG group over the time-course of the study, especially in the LST group, which showed exuberant granulation tissue with intense vascularization, and deposition of newly formed collagen fibers (3 and 7 days). It was concluded that the LLLT presented an anti-nociceptive and anti-inflammatory response on the inflammation induced in the temporomandibular joint of rodents., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Purpose: The aim of this study was to compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with achillodynia., Patients and Methods: Between February 2006 and February 2010, 112 consecutive evaluable patients were recruited for this prospective randomized trial. All patients underwent radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions over 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy with a visual analogue scale (VAS) and a comprehensive pain score (CPS)., Results: The overall response rate for all patients was 84% directly after and 88% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 55.7 ± 21.0 and 58.2 ± 23.5 (p = 0.526), 38.0 ± 23.2 and 30.4 ± 22.6 (p = 0.076), and 35.4 ± 25.9 and 30.9 ± 25.4 (p = 0.521), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 8.2 ± 3.0 and 8.9 ± 3.3 (p = 0.239), 5.6 ± 3.1 and 5.4 ± 3.3 (p = 0.756), 4.4 ± 2.6 and 5.3 ± 3.8 (p = 0.577), respectively. No statistically significant differences were found between the two single-dose trial arms for early (p = 0.366) and delayed response (p = 0.287)., Conclusion: Radiotherapy is an effective treatment option for the management of achillodynia. For radiation protection, the dose of a radiotherapy series is recommended not to exceed 3-6 Gy.

Background and Purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome., Patients and Methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS)., Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380)., Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy.

Background and Purpose: The goal of the present study was to evaluate the efficacy of two different dose-fractionation schedules for radiotherapy (RT) of patients with painful elbow syndrome., Patients and Methods: Between February 2006 and February 2010, 199 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received RT in orthovoltage technique. One RT course consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after RT by a visual analogue scale (VAS) and a comprehensive pain score (CPS)., Results: The overall response rate for all patients was 80% direct after and 91% 6 weeks after RT. The mean VAS values before, after and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 59.6 ± 20.2 and 55.7 ± 18.0 (p = 0.463), 32.1 ± 24.5 and 34.4 ± 22.5 (p = 0.256), and 27.0 ± 27.7 and 23.5 ± 21.6 (p = 0.818). The mean CPS before, after, and 6 weeks after treatment was 8.7 ± 2.9 and 8.1 ± 3.1 (p = 0.207), 4.5 ± 3.2 and 5.0 ± 3.4 (p = 0.507), 3.9 ± 3.6 and 2.8 ± 2.8 (p = 0.186), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.103) and delayed response (p = 0.246) were found., Conclusion: RT is an effective treatment option for the management of benign painful elbow syndrome. For radiation protection reasons the dose for a RT series is recommended not to exceed 3.0 Gy.

UV-irradiation is a well-known translational pain model inducing local inflammation and primary hyperalgesia. The mediators and receptor proteins specifically contributing to mechanical or heat hyperalgesia are still unclear. Therefore, we irradiated buttock skin of humans (n = 16) with 5-fold MED of UV-C and assessed the time course of hyperalgesia and axon reflex erythema. In parallel, we took skin biopsies at 3, 6 and 24 h after UVC irradiation and assessed gene expression levels (RT-PCR ) of neurotrophins (e.g. NGF, BDNF, GDNF), ion channels (e.g. NaV1.7, TRPV1), inflammatory mediators (e.g. CCL-2, CCL-3) and enzymes (e.g. PGES, COX2). Hyperalgesia to mechanical impact (12 m/s) and heat (48 °C) stimuli was significant at 6 h (p<0.05 and p<0.01) and 24 h (p<0.005 and p<0.01) after irradiation. Axon reflex erythema upon mechanical and thermal stimuli was significantly increased 3 h after irradiation and particularly strong at 6 h. A significant modulation of 9 genes was found post UV-C irradiation, including NGF (3, 6, 24 h), TrkA (6, 24 h), artemin, bradykinin-1 receptor, COX-2, CCL-2 and CCL-3 (3 and 6 h each). A significant down-regulation was observed for TRPV1 and iNOS (6, 24 h). Individual one-to-one correlation analysis of hyperalgesia and gene expression revealed that changes of Nav1.7 (SCN9A) mRNA levels at 6 and 24 h correlated to the intensity of mechanical hyperalgesia recorded at 24 h post UV-irradiation (Pearson r: 0.57, p<0.04 and r: 0.82, p<0.001). Expression of COX-2 and mPGES at 6 h correlated to the intensity of heat-induced erythema 24 h post UV (r: 0.57, p<0.05 for COX-2 and r: 0.83, p<0.001 for PGES). The individual correlation analyses of functional readouts (erythema and pain response) with local expression changes provided evidence for a potential role of Nav1.7 in mechanical hyperalgesia.

Purpose: This study evaluated the tolerance and therapeutic efficacy of rhenium-188 hydroxyethylidene diphosphonate ((188)Re-HEDP) in patients with different types of advanced cancer suffering from bone pain caused by osseous metastases., Methods: Sixty-four patients received a single injection of escalating doses of (188)Re-HEDP with various dosages. Vital signs were observed before and after treatment for 8 weeks; adverse effects and rebound pain were recorded within 8 weeks after injection. Blood counts, biochemical parameters, and electrocardiogram were also measured over a period of 8 weeks. Clinical follow-up studies including the bone pain score and the Karnofsky performance score were performed. Pain response was scored by a four-point pain-rating scale as complete, marked, mild, and no response., Results: No adverse effects or clinically significant changes in vital signs, electrocardiograms, and biochemical parameters in patients were observed, and there was no statistical change in alkaline phosphate levels in patients before or after treatment. The overall nadir of thrombopenia was at week 4, leucopoenia at week 3, and anemia at week 8. At week 8, the mean level of platelets and leukocytes returned to baseline levels. The pain score descended from 8.11 to 7.74 on the day of therapy, with a nadir of 4.89 at week 4, and up to 6.67 at week 8 after therapy (p < 0.05). The Karnofsky performance score continually increased from 74.81 before therapy to 82.31 at 8 weeks (p > 0.05 Pain palliation was reported by 73.33% of patients, with a mean duration of 6.85 weeks and a mean start time of 4.05 days. Of the specific tumor types, pain relief was achieved in 84.62% of patients with prostate cancer, 78.57% with breast cancer, 62.50% with lung cancer, and 55.56% with liver cancer., Conclusions: (188)Re-HEDP is a useful radiopharmaceutical agent for improving bone pain in patients with advanced cancer with painful bone metastases.

Background: The Gorham-Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide., Case Report: A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization., Conclusion: Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40-45 Gy are recommended.

Background and Purpose: After a patterns-of-care study (PCS) in 2003/2004 addressing benign disorders in general, the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) conducted several multicenter cohort studies including the use of radiotherapy (RT) in painful gonarthrosis (GNA)., Material and Methods: From 2006 to 2008, a PCS for GNA was conducted in all German RT institutions using a standardized structured questionnaire. Patient accrual, patient number, pretreatment, pain record, treatment indications, RT technique, and target volume concepts for painful GNA were assessed. In addition, the long-term functional and subjective outcomes were evaluated., Results: 238/248 institutions (95.9%) returned the questionnaire: 50 (21%) reported no clinical experience with RT in GNA, while 188 (79%) institutions treated 4,544 patients annually (median 15; range one to 846 cases per institution). Indications for treatment were acute pain symptoms in 18.9%, chronic pain in 95.3%, and treatment-refractory pain in 81.1%. The median total dose was 6 Gy (range 3-12 Gy), with a median single dose of 1 Gy (0.25-3 Gy). 40.4% of the institutions applied two fractions and 51.4% three fractions weekly. RT was delivered with orthovoltage units (25%), linear accelerators (79.6%), and cobalt-60 units (8.3%). 42 institutions evaluated the long-term clinical outcome in a total of 5,069 cases. Median pain reduction for at least 3 months was reported in 60% (5-100%), median pain reduction for at least 12 months in 40% (10-100%), and median persistent pain reduction in 27.8% (10-85%) of the treated patients. In 30% of patients (7-100%), a second RT series was applied for inadequate pain response or early pain recurrence. No radiogenic acute or chronic side effects were observed., Conclusion: This PCS comprises the largest number of cases reported for RT in painful and refractory GNA. Despite variations in daily RT practice, high response and low toxicity for this treatment in a very large number of painful and refractory GNA cases renders low-dose RT an effective conservative therapy which can be applied prior to surgical procedures.

Purpose: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML])., Patients and Methods: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovoltage X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS)., Results: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted., Conclusion: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder.

Background and Purpose: Calcifying tendonitis is a degenerative inflammatory joint disorder. Pain relief can be successfully achieved with low-dose radiotherapy. It is actually unknown which types of calcifying tendonitis respond to radiotherapy and which do not. The authors tried to get predictive objectives for the response to radiotherapy on the basis of different morphological patterns of calcifications evaluated by X-ray and ultrasound., Patients and Methods: Between August 1999 and September 2002, a total of 102 patients with 115 painful shoulder joints underwent low-dose radiotherapy. At the beginning of radiotherapy, every shoulder joint was examined with a radiograph in two planes. In addition, sonography was performed before and during therapy. This examination was repeated 6 and 18 months after irradiation. Radiotherapy consisted of two series with a total dose of 6.0 Gy. 29 joints with calcifying tendonitis could be further divided using the sonographic and radiographic classification according to Farin and Gärtner, respectively., Results: Pain relief was achieved in 94/115 joints (82%) at a follow-up of 18 months (median). A different response to radiotherapy was found using the sonographic classification of Farin: calcifying tendonitis type III (n = 18) responded well in contrast to a significantly worse result in type I (n = 11). The radiologic classification did not provide a predictive value., Conclusion: Sonographic classification of calcifying tendonitis is predictive for the outcome after radiotherapy. Especially patients with Farin type III calcification will benefit from low-dose radiotherapy.

Aim: The aim of this study was to assess the usefulness of (153)samarium-ethylene-diamino-tetramethylene phosphonic acid ((153)Sm-EDTMP, a beta and gamma emitter) treatment in the palliation of painful bone metastases from breast cancer., Patients and Methods: 43 women (aged 41-79, mean 60 years) with bone-disseminated breast cancer and bone pain refractory to opioid analgesics received (153)Sm-EDTMP. Karnofsky performance status, pain score (numeric rating scale), analgesic score (World Health Organisation) and blood count were evaluated before treatment and 1 and 3 months after the treatment., Results: Significant pain relief was observed in 51 and 42% of the patients, mild relief in 30 and 30%, and no effect in 19 and 28% of the patients 1 and 3 months after administration, respectively. Mild and transient bone marrow suppression was observed as a side effect of (153)Sm-EDTMP treatment. None of the patients showed grade 4 haematological toxicity and only 1 patient showed grade 3 (National Cancer Institute common toxicity criteria). The majority of patients had grade 1 or 2 haematological toxicity., Conclusion: (153)Sm-EDTMP treatment is effective and safe in bone pain palliation in breast cancer. 3 months after administering (153)Sm-EDTMP, pain relief to varying degrees was observed in 72% of patients.The haematological toxicity after (153)Sm-EDTMP treatment was mild and transient., (Copyright (c) 2009 S. Karger AG, Basel.)

Previous experiments with mice have shown that repeated 1 hour daily exposure to an ambient magnetic field-shielded environment induces analgesia (antinociception). The exposures were carried out in the dark (less than 2.0x1016 photonss-1m-2) during the mid-light phase of the diurnal cycle. However, if the mice were exposed in the presence of visible light (2.0x1018 photonss-1m-2, 400-750 nm), then the analgesic effects of shielding were eliminated. Here, we show that this effect of light is intensity and wavelength dependent. Introduction of red light (peak at 635 nm) had little or no effect, presumably because mice do not have photoreceptors sensitive to red light above 600 nm in their eyes. By contrast, introduction of ultraviolet light (peak at 405 nm) abolished the effect, presumably because mice do have ultraviolet A receptors. Blue light exposures (peak at 465 nm) of different intensities demonstrate that the effect has an intensity threshold of approximately 12% of the blue light in the housing facility, corresponding to 5x1016 photonss-1m-2 (integral). This intensity is similar to that associated with photoreceptor-based magnetoreception in birds and in mice stimulates photopic/cone vision. Could the detection mechanism that senses ambient magnetic fields in mice be similar to that in bird navigation?

To investigate whether laser acupuncture is efficacious in children with headache and if active laser treatment is superior to placebo laser treatment in a prospective, randomized, double-blind, placebo-controlled trial of low level laser acupuncture in 43 children (mean age (SD) 12.3 (+/-2.6) years) with headache (either migraine (22 patients) or tension type headache (21 patients)). Patients were randomized to receive a course of 4 treatments over 4 weeks with either active or placebo laser. The treatment was highly individualised based on criteria of Traditional Chinese medicine (TCM). The primary outcome measure was a difference in numbers of headache days between baseline and the 4 months after randomization. Secondary outcome measures included a change in headache severity using a 10 cm Visual Analogue Scale (VAS) for pain and a change in monthly hours with headache. Measurements were taken during 4 weeks before randomization (baseline), at weeks 1-4, 5-8, 9-12 and 13-16 from baseline. The mean number of headaches per month decreased significantly by 6.4 days in the treated group (p<0.001) and by 1.0 days in the placebo group (p=0.22). Secondary outcome measures headache severity and monthly hours with headache decreased as well significantly at all time points compared to baseline (p<0.001) and were as well significantly lower than those of the placebo group at all time points (p<0.001). We conclude that laser acupuncture can provide a significant benefit for children with headache with active laser treatment being clearly more effective than placebo laser treatment.

The present study deals with the analgesic effect induced by static magnetic fields (SMF) in mice exposed to the field with their whole body. It discusses how the effect depends on the distribution of the magnetic field, that is, on the specification and arrangement of the applied individual permanent magnets. A critical analysis of different magnet arrangements is given. As a result the authors propose a magnet arrangement recipe that achieves an analgesic effect of over 80% in the writhing test. This is a widely accepted screening method for animal pain and predictor of human experimental results. As a non-drug, non-invasive, non-contact, non-pain, non-addictive method for analgesia with immediate and long-lasting effect based on the stimulus of the endogenous opioid network, the SMF treatment may attract the attention of medical doctors, nurses, magnet therapists, veterinarians, physiotherapists, masseurs, and fitness trainers among others., ((c) 2007 Wiley-Liss, Inc.)

We assessed the pain-relieving efficacy of static magnetic fields produced by 200 Gauss (G) magnets compared with 50G magnets in a double-blind, randomized, two-phase crossover study in patients with chronic lumbar radicular pain. The surface field strengths of the magnets were 200 and 50G. Phase I included four random periods of two-week duration: two periods with 200G, one period with 50G, and one period of "no treatment." The magnets were positioned either vertically or horizontally in standard lumbosacral elastic corsets. Phase II consisted of two five-week periods with the most effective magnet from Phase I and its corresponding 50 or 200G device. The primary outcome was average daily leg pain score (0-10 scale) in each period of Phase II. Thirty-eight of 40 randomized patients completed Phase I, and 28 of 31 Phase II participants completed the study. In Phase I, pain scores did not differ significantly between 200 and 50G magnets. Phase II average leg pain scores tended to be lower with 200 vs. 50G magnets (3.2+/-2.1 for 200G vs. 3.9+/-2.2 for 50G magnets [P=0.08]) after excluding one unblinded patient. The relative treatment effect of the 200G magnets appeared to increase throughout the five-week period. Although these data cannot rule out a chance effect, the positive trends suggest that larger, longer-duration, sham-controlled trials with 200G magnets be considered in patients with chronic lumbar radicular pain.

Objectives: The aim of this study was to evaluate the efficacy of a systemic application of rhenium-186 hydroxyethylidenediphosphonate (Re HEDP) for pain treatment in patients with hemophilic arthropathies., Methods: Twelve patients with hemophilic arthropathy with at least 3 involved joints with persistent pain were included in this prospective study. A single dose of 15 mCi (555 MBq) Re HEDP was administered intravenously. Before and 12 weeks after treatment, pain assessment was performed using the visual analog scale (VAS). The pain status assessment included the general status, pain of all joints affected, and pain of the 3 mostly involved joints. Furthermore, quality of life was assessed., Results: With regard to the 3 most involved joints, an improvement of the pain symptoms in 25 of 36 (69.4%) joints was observed. With regard to all involved joints a median of 3 joints per patient improved after Re HEDP therapy. General pain status after treatment was 2.0 VAS points lower as compared with pretreatment. The total number of involved joints remained unchanged in 7 patients, increased in 1 patient, and decreased in the remaining 4 patients., Conclusions: The results of this study show an improvement of the pain symptoms of the involved joints 12 weeks after therapy with Re HEDP in patients with hemophilic arthropathy. The only moderate success regarding a reduction of the total number of involved joints is by the fact that despite this improvement most affected joints remained still painful on a lower level after the therapy or due to newly affected joints not painful before initiation of the radionuclide therapy.

The objective was to test whether exposure to radio frequency (RF) fields from mobile phones may cause head pain or discomfort and whether it may influence physiological variables in individuals attributing symptoms to mobile phones, but not to electromagnetic fields in general. Seventeen eligible individuals, who experienced these symptoms in an open provocation test, took part in a double-blind, randomized provocation study with cross-over design. Sixty-five pairs of sham and mobile phone RF exposures were conducted. The increase in pain or discomfort (visual analogue scales) in RF sessions was 10.1 and in sham sessions 12.6 (P=0.30). Changes in heart rate or blood pressure were not related to the type of exposure (P: 0.30-0.88). The study gave no evidence that RF fields from mobile phones may cause head pain or discomfort or influence physiological variables. The most likely reason for the symptoms is a nocebo effect.

Objective: The authors conducted a comparative study to analyze dosimetry and results to understand the significant difference in the rate of trigeminal dysfunction after gamma knife radiosurgery for trigeminal neuralgia between two centers using the same target., Methods: The data of 358 patients (109 patients from Brussels and 259 patients from Marseilles) were analyzed. Three different dosimetric strategies were found: treatment with less than 90 Gy and no selective beam channel blocking (Group 1; patients from Marseilles only), treatment with 90 Gy and no selective beam channel blocking (Group 2; patients from Brussels and Marseilles), or treatment with 90 Gy and use of selective beam channel blocking (Group 3; patients from Brussels only)., Results: The prescription dose and the use of selective beam channel blocking have been significantly associated with a higher energy received by the retrogasserian trigeminal nerve root. The different radiation dose delivered to the nerve root in these three groups of patients was significantly associated with the incidence of mild (15, 21, and 49% for Groups 1, 2, and 3, respectively) and bothersome (1.4, 2.4, and 10% for Groups 1, 2, and 3, respectively) trigeminal dysfunction. The good and excellent rates of pain relief were 81 and 66%, respectively, for Group 1, 85 and 77%, respectively, for Group 2, and 90 and 84%, respectively, for Group 3, and were also related to the amount of energy received by nerve root volume., Conclusion: Using a similar target, the incidence of trigeminal dysfunction and the pain relief rate can vary according to the radiation energy received by the retrogasserian part of the trigeminal nerve root. The prescription dose and the use of beam channel blocking modify the integrated dose delivered to the nerve and may contribute to the different rates of trigeminal numbness and pain outcome. The radiobiological effect of gamma knife radiosurgery may be related to the energy delivered to nerve root volume, rather than to the maximal dose delivered.

Static and pulsed magnetic fields have been reported to have a variety of physiological effects. However, the effect of static magnetic fields on pain perception and sympathetic function is equivocal. To address this question, we measured pain perception during reproducible noxious stimuli during acute exposure to static magnets. Pain perception, muscle sympathetic nerve activity, mean arterial pressure, heart rate, and forearm blood velocity were measured during rest, isometric handgrip, postexercise muscle ischemia, and cold pressor test during magnet and placebo exposure in 15 subjects (25 +/- 1 yr; 8 men and 7 women) following 1 h of exposure. During magnet exposure, subjects were placed on a mattress with 95 evenly spaced 0.06-T magnets imbedded in it. During placebo exposure, subjects were placed on an identical mattress without magnets. The order of the two exposure conditions was randomized. At rest, no significant differences were noted in muscle sympathetic nerve activity (8 +/- 1 and 7 +/- 1 bursts/min for magnet and placebo, respectively), mean arterial pressure (91 +/- 3 and 93 +/- 3 mmHg), heart rate (63 +/- 2 and 62 +/- 2 beats/min), and forearm blood velocity (3.0 +/- 0.3 and 2.6 +/- 0.3 cm/s). Magnets did not alter pain perception during the three stimuli. During all interventions, no significant differences between exposure conditions were found in muscle sympathetic nerve activity and hemodynamic measurements. These results indicate that acute exposure to static magnetic fields does not alter pain perception, sympathetic function, and hemodynamics at rest or during noxious stimuli.

Purpose: To evaluate the efficacy of two different dose-fractionation schedules for radiation therapy (RT) in patients with painful heel spurs., Patients and Methods: 130 patients were randomized into two groups: the low-dose (LD) group (n = 65 heels) received a total dose of 3.0 Gy given in two weekly fractions of 0.5 Gy; in the high-dose (HD) group (n = 65 heels), two weekly fractions of 1.0 Gy were applied over 3 weeks (total dose 6.0 Gy). In 24 sites of the HD group and 17 sites of the LD group, a second RT course was given. The results were assessed using a five-level function score which was documented before RT, at the end of each RT course, and at 6 weeks and 6 months thereafter., Results: At 6-month follow-up, RT led to a highly significant reduction of symptoms in both groups. In the HD group, 31 sites were classified as excellent (score: 90-100), 13 as good (score: 70-85), twelve as moderate (score: 45-65), and nine as poor (score: 0-40). In the LD group, 35 sites were classified as excellent, eight as good, ten as moderate, and twelve as poor. The comparison of the difference of the sum score and the single criteria before RT and at 6 months after RT using the Wilcoxon-Mann-Whitney U-test revealed no statistically significant difference of response to RT between both groups., Conclusion: RT is an effective treatment option for the management of inflammatory heel spurs. The dose for an RT course should not exceed 3.0 Gy.

Aim: Palliative therapy using [186Re]hydroxyethylidene diphosphonate (HEDP) has been widely tested in patients with bone metastases from prostate and breast cancers. Whereas, to the best of our knowledge, only few cases of bone metastases from tumors other than prostate and breast treated with [186Re]HEDP have been reported. The aim of this paper is to report our experience with 186Re-HEDP in the palliation of painful bone metastases from tumors other than prostate and breast., Methods: In this study 41 patients (17 non-small cell lung cancer-NSCLC, 1 small cell lung cancer, 1 lung neuroendocrine tumor, 8 bladder cancer, 3 kidney cancer, 3 gastric cancer, 1 uterine carcinoma, 1 colon cancer, 1 rhinopharynx carcinoma, 1 medullary thyroid carcinoma, 1 ovarian cancer, 1 esophagus cancer, 2 carcinoma of unknown origin) are evaluated. All patients had lesions with increased [99mTc]MDP uptake and none had radiological findings of mainly osteolytic lesions. A total of 46 therapeutic cycles were performed using a [186Re]HEDP activity of 1 295 MBq for each administration. After treatment, patients were followed up for 3 months or to the time of pain recurrence (if longer than 3 months). Responses were evaluated using a validated method considering the modifications of pain index, analgesic intake and performance status., Results: Treatment efficacy was complete in 49% (20/41) of patients, partial in 36% (15/41) and negative in 15% (6/41). Namely, we observed 35% (6/17) complete, 41% (7/17) partial and 24% (4/17) negative responses in patients with NSCLC and 63% (5/8) complete, 25% (2/8) partial and 12% (1/8) negative responses in patients affected by bladder cancer. The median duration of pain relief in responder patients was 10 weeks. A mild platelet toxicity occurred in 32% (13/41) of patients., Conclusions: Pain palliation with [186Re]HEDP seems highly effective and safe also in patients with bone metastases from cancers other than prostate and breast. Patients who can benefit from the treatment with [186Re]HEDP can be selected on the basis of [99mTc]MDP bone scan and radiological examination findings.

Background: Intradiscal radiofrequency, with the electrode placed in the center of the nucleus pulposus, has been a controversial procedure in patients with discogenic pain. Possibly the effect has not been due to the production of heat, but to exposure to electric fields., Design: We have investigated the effect of high-voltage, long-duration intradiscal pulsed radiofrequency in patients with one-level discogenic low back pain, as confirmed by discography., Outcome Measure: The pain intensity score on a 0-10 numeric rating scale (NRS) was taken as outcome measure., Patients: Eight patients were reported. The mean duration of pain was 6.3 years (range 0.5-16, median 4). The mean NRS score was 7.75 (range 5-9). Disc height was reduced 60% in one patient and up to 30% in the others., Intervention: A 15-cm, 20-gauge needle with a 15-mm active tip was placed centrally in the disc. Pulsed radiofrequency was applied for 20 min at a setting of 2 x 20 ms/s and 60 V., Results: There was a very significant fall in the NRS scores over the first 3 months (P < 0.0001). On an individual basis, all patients had a fall of the NRS score of at least 4 points at the 3-month follow-up. A follow-up of 12.8 months (range 6-25, median 9) was available for five patients. All these patients are now pain free, except for one patient with an NRS score of 2. Conclusion. It is concluded that this method merits a controlled, prospective study.

Objective: Current therapies for sacroiliac joint (SIJ) dysfunction offer discouraging results in alleviating low back pain. The innervation and target nerves for radiofrequency denervation (RFD) of the SIJ remain unclear. We present a prospective case series on the treatment of intractable SIJ dysfunction with pulsed radiofrequency denervation (PRFD) of lateral branches from L4-S3., Interventions: A total of 126 patients with presumptive SIJ dysfunction based on history and physical examination underwent arthrographically confirmed steroid/local anesthetic SIJ injection. Fifty-two patients (41.3%) had >75% pain relief after two consecutive injections, physical therapy, repeated SIJ injections, and/or analgesics. Twenty-two patients failed to respond. These patients underwent PRFD of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2., Outcome Measures: Visual analog score (VAS) and quality of life (QOL) assessments were performed prior to and after treatment., Results: Sixteen patients (72.7%) experienced "Good" (>50% reduction in VAS), or "Excellent" (>80% reduction in VAS) pain relief following PRFD. Duration of pain relief range was 6-9 weeks in four patients, 10-16 weeks in five patients, and 17-32 weeks in seven patients. In addition, QOL scores improved significantly in all measured categories. Six patients (26.1%) did not respond to PRFD and had less than 50% reduction in VAS and were considered failures., Conclusions: PRFD of the lateral branch of the medial branch of L4, posterior primary rami of L5, and lateral branches S1 and S2 is an effective treatment for some patients with SIJ pain unresponsive to other forms of therapy.

Radiant heat is often used for studying thermal nociception, although inherent characteristics such as the broad spectrum of applied wavelengths of typical light sources limit control over and repeatability of stimuli. To overcome these problems, we used a diode infrared laser-based stimulator (wavelength: 980 nm) for selectively stimulating trigeminal Adelta or C thermonociceptors in rats. To provide indirect evidence for nociceptor-selective stimulation, we tested the effects of capsaicin, dimethylsulfoxide (DMSO), and morphine on withdrawal latencies for long pulses with a low current (hypothesized to selectively stimulate C nociceptors) and for threshold currents of short pulses with high current (hypothesized to selectively stimulate Adelta nociceptors) in lightly anesthetized rats. Nonmem analysis was used to perform pharmacodynamic modeling. The measured baseline withdrawal latency for long pulses was 12.5 +/- 0.3 s which was changed significantly to 6.7 +/- 0.4 s after applying topical capsaicin which selectively sensitizes C nociceptors and to 16.5 +/- 1.3 s after 1.0 mg/kg morphine which preferentially attenuates C fiber nociception. Topical DMSO which appears to selectively sensitize Adelta afferents did not significantly alter withdrawal latencies to the long pulses. Fitted threshold currents for short pulses after DMSO were however significantly lower (974 +/- 53 mA vs. 1113 +/- 12 mA for baseline) indicating Adelta sensitization. Capsaicin and morphine did not significantly change threshold currents. Best Nonmem fits for the long pulse were obtained using a model assuming no DMSO effect, but a different inter-individual variability after applying this substance. For the short pulse, a model assuming no capsaicin or morphine effect, but again allowing different inter-individual variabilities after applying these drugs, best described the data. We conclude that different settings of the stimulator used in this study were capable of selectively activating trigeminal Adelta or C thermonociceptors.

Alterations in the intracellular signal transduction pathway in primary afferents may contribute to pain hypersensitivity. We demonstrated that very rapid phosphorylation of p38 mitogen-activated protein kinase occurred in dorsal root ganglion (DRG) neurons that were participating in the transmission of noxious signals. Capsaicin injection induced phosphorylated-p38 (p-p38) in small-to-medium diameter sensory neurons with a peak at 2 min after capsaicin injection. Furthermore, we examined the p-p38 labeling in the DRG after noxious thermal stimuli and found a stimulus intensity-dependent increase in labeled cell size and the number of activated neurons. Most of these p-p38-immunoreactive (IR) neurons were small- and medium-sized neurons, which coexpressed transient receptor potential ion channel TRPV1 and phosphorylated-extracellular signal-regulated protein kinase. Intrathecal administration of the p38 inhibitor, FR167653, reversed the thermal hyperalgesia produced by the capsaicin injection. Inhibition of p38 activation was confirmed by the decrease in the number of p-p38-IR neurons in the DRG following capsaicin injection. Taken together, these findings suggest that the activation of p38 pathways in primary afferents by noxious stimulation in vivo may be, at least in part, correlated with functional activity, and further, involved in the development of thermal hyperalgesia.

Exposure to pulsed magnetic fields (MF) has been shown to have a therapeutic benefit in both animals (e.g. mice, snails) and humans. The current study investigated the potential analgesic benefit of MF exposure on sensory and pain thresholds following experimentally induced warm and hot sensations. Thirty-nine subjects (Study 1) and 31 subjects (Study 2) were randomly and double-blindly assigned to 30 min of MF or sham exposure between two sets of tests of sensory and pain thresholds and latencies at, 1 degrees C above, and 2 degrees C above pain thresholds. Results indicated that MF exposure does not affect sensory thresholds [e.g. [F(1,31) = 0.073, NS]. Pain thresholds were significantly increased following MF exposure [F(1,6) = 9.45, P < 0.01] but not following sham exposure [F (1,4) = 4.22, NS]. A significant condition by gender interaction existed for post-exposure pain thresholds [F(1,27) = 5.188, P < 0.05]. Taken together, these results indicate that MF exposure does not affect basic human perception, but can increase pain thresholds in a manner indicative of an analgesic response. The potential involvement of the placebo effect is discussed.

Results of previous studies have shown that nociceptive sensitivity in male C57 mice is enhanced by exposure to a regular 37 Hz or an irregularly varying (<1 Hz) electromagnetic field. In order to test whether these fields affect more generally mouse behaviour, we placed Swiss CD-1 mice in a novel environment (open field test) and exposed them for 2 h to these two different magnetic field conditions. Hence, we analysed how duration and time course of various behavioural patterns (i.e. exploration, rear, edge chew, self-groom, sit, walk and sleep) and nociceptive sensitivity had been affected by such exposure. Nociceptive sensitivity was significantly greater in magnetically treated mice than in controls. The overall time spent in exploratory activities was significantly shorter in both magnetically treated groups (< 1 Hz, 33% and 37 Hz, 29% of total time), than in controls (42%). Conversely, the time spent in sleeping was markedly longer in the treated groups (both 27% of total time) than in controls (11%). These results suggest that exposure to altered magnetic fields induce a more rapid habituation to a novel environment.

Previous studies have shown that exposure to altered magnetic fields alters analgesic responses in a variety of species, including humans. Here we examined whether deprivation of the normally occurring geomagnetic field also affects stress-induced analgesia, by measuring the nociceptive responses of C57 male mice that were restraint-stressed in a hypogeomagnetic environment (inside a mu-metal box). Stress-induced analgesia was significantly suppressed in a manner comparable to that observed in mice that were either exposed to altered oscillating magnetic fields or treated with the prototypic opiate antagonist naloxone. These results represent the first piece of evidence that a period in a hypogeomagnetic environment inhibits stress-induced analgesia.

To evaluate the therapeutic effect of IORT for unresectable locally advanced pancreatic cancer, 11 patients treated with IORT and 15 patients treated with palliative therapy only were retrospectively examined. The mean age of the IORT group was 61.9 years, 5 cases were classified into surgical stage IVa, and 6 into stage IVb. The mean age of the palliative therapy group was 69.1 years; 5 cases were classified into surgical stage IVa and 10 into stage IVb. The tumor size was measured in 6 cases in the IORT group, before and after IORT. The tumor was enlarged in 1 case, not changed in 4 cases, and reduced in 1 case. The serum CA19-9 level was measured in 8 cases of the IORT group. Serum CA19-9 was increased in 3 cases, not changed in 4 cases, and decreased in 1 case after IORT. ECOG pain scores were obtained in 9 patients who had complained of pain before IORT, and the score decreased in 7 cases. The median survival was 7.6 months in the IORT group and 3.0 months in the palliative therapy group. IORT may improve patients' QOL by decreasing their pain. However, further studies are necessary to confirm the efficacy of IORT for survival of locally unresectable pancreatic cancer patients, because the patient profile in this study was different in the two groups.

The present experiments sought to establish dose dependency and time course for effects of cranial laser irradiation in two rodent models of pain. These were the hot plate and tail flick tests, which are both widely used to quantify analgesic drug effects. The laser used was an Omega Biotherapy 3ML (wavelength 820 nM, average power output 100 mW, pulse frequency 5 kHz) and irradiation was applied to rats' shaved heads above the midbrain. In the first experiment, four groups of 10 rats received doses of 0, 6, 12, 18, and 24 J/cm2 in random orders prior to hot plate testing either immediately, 30 min, 1 h or 24 h postlaser. The second study employed three groups of 10 rats receiving 0, 12, and 18 J/cm2 in random orders prior to tail flick testing at the three shorter times above. Latency to lick hind paws on the hot plate was highly significantly prolonged by laser treatment across all doses and time periods, F(4, 126) = 4.51, p < 0.01. There was good dose dependency for immediate observations, but at 24 h 18 J/cm2 was the most effective dose. Laser treatment also delayed tail flick responses at both doses and all time periods, F(2, 54) = 10.60, p < 0.001, but 12 and 18 J/cm2 doses were similar in efficacy.

A total of 223 patients with 498 symptomatic osseous metastases treated by radiotherapy between July 1985 and June 1991 were retrospectively analyzed. Most sites, 409 (82%), were irradiated by conventional fractionation, while the remaining 89 sites were irradiated by dose-increment fractionation, low-dose short schedules or hyperfractionation. The total dose ranged from 5.4 to 74 Gy (mean, 41.4 Gy). Daily pain assessment was done by patients themselves on an 11-point scale, i.e., 10: pretreatment pain, 0: disappearance of pain following radiotherapy. In addition, improvement in performance status (PS) and the duration of complete pain relief were assessed. The following results were obtained. 1) Pain relief: Of 498 evaluated sites, complete pain relief and partial pain relief were achieved in 403 sites (81%) and 64 sites (13%), respectively. No significant difference was seen in the incidence of complete pain relief between weight-bearing bone and non-weight-bearing bone. Patients with PS 1, 2 or 3 were significantly superior to those with PS 4 in terms of complete pain relief (P < 0.05-0.001). The complete response rate increased in accordance with the dose delivered, i.e., 49% at 20 Gy, 70% at 30 Gy and 77% at 40 Gy, in all of the 498 sites irradiated; 60%, 86% and 95% of 403 sites, respectively, achieved complete pain relief. Regarding the fractionation regimens, dose-increment fractionation was superior to both conventional fractionation and low-dose short schedules in terms of complete pain relief rate. 2) Improvement of PS: Of 223 evaluated patients, PS was improved 1 to 3 steps in 162 (73%) at the completion of radiotherapy. The improvement rates of patients with PS 2 or 3 were significantly better than those with PS 4 (P < 0.025, 0.001). 3) Duration of complete pain relief: Of 288 appraisable sites, the recurrence of pain was recognized in 23 (9%) at intervals of 3 to 21 months (median, 5 months). On the other hand, the duration of pain relief was 16 to 79 months (median, 32 months) in 26 sites of survivors, and 1 to 28 months (median, 5 months) in 239 sites of decreased patients. The mean total dose was 48.5 Gy (TDF: 82) to 62 sites with a duration of pain relief of more than 13 months. 4) Re-irradiation to the same site: Of 14 sites retreated after initial complete response with a total dose of 30 to 50 Gy (mean, 48 Gy), 11 (79%) were in weight-bearing bone and 9 (64%) responded completely. 5) Patients with unsatisfactory pain relief (pain score > or = 6): Of 31 sites, 27 (94%) were in patients with PS 4, and 19 (61%) received a total dose below 30 Gy. 6) The 11-point scale for patient self-assessment of pain relief following radiotherapy was thought to be useful and easy to adopt in general clinics.