Search

The objective of this study was to evaluate if a single session of real or placebo cupping therapy in patients with chronic low back pain would be enough to temporarily reduce pain intensity and functional disability, enhancing their mechanical threshold and reducing local skin temperature. The outcome measures were Brief Pain Inventory, pressure pain threshold, Roland-Morris disability questionnaire and low back skin temperature. This is an experimental clinical trial; after examination (AV0), patients were submitted to real or placebo cupping therapy (15 minutes, bilaterally at the points BL23 (Shenshu), BL24 (Qihaishu) and BL25 (Dachangshu) and were revaluated immediately after the session (AV1) and after one week (AV2). The patients showed a significant improvement in all pain severity items and sleep in the Brief Pain Inventory (p 0.05) and a decrease in disability in Roland-Morris disability questionnaire (p 0.001). No significant differences were found in pressure pain threshold or skin temperature. No significant differences were found in any outcome of the placebo cupping therapy group. Thus, the cupping therapy is effective in reducing low back pain and decreasing disability after one single session but not in changing skin mechanical threshold or temperature.

Background and aims Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period. Methods The animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2–15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund’s complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later. Results Maternal behavior and litter weight were not altered by pinprick stimuli during PND 2–15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA-injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase. Conclusions Experiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation. Implications Future investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences.

Animals subjected to early life maternal separation exhibit increased sensitivity to chemical, thermal, and mechanical stimuli during adulthood. However, the mechanism by which maternal separation can alter pain sensitivity in adulthood has not yet been investigated. Thus, we aimed to evaluate the activity of serotonergic and noradrenergic neurons and the effect of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors in male and female Wistar rats subjected to maternal separation. This study consisted of two experiments: 1) to confirm whether maternal separation increased pain sensitivity (n = 8 per group) and to evaluate the activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in locus coeruleus in animals subjected to maternal separation in comparison to controls (n = 6 per group); and 2) to evaluate the effect of fluoxetine (a selective 5-HT reuptake inhibitor) and desipramine (a NA reuptake inhibitor) on sensitivity to chemical stimulation using formalin in animals subjected to maternal separation (n = 8 per group). Our findings indicated that maternal separation increases an animal's sensitivity to painful chemical stimulation and reduces the activity of 5-HT and NA neurons. In addition, acute pretreatment with a 5-HT or NA reuptake inhibitor prevented the increased response to painful stimulation induced by maternal separation. In conclusion, maternal separation increases pain sensitivity by reducing the activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in locus coeruleus. This study contributes to possible treatments for pain in individuals exposed to early life stress.

Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological procedure may also cause antinociception in rodents with neuropathic pain. Cold allodynia is a frequent clinical finding in patients with neuropathic pain, then, we evaluated if an adapted model of neuropathy induced by chronic constriction injury (CCI) of the ischiadicus nervus (sciatic nerve) produces cold allodynia in an animal model of chronic pain. In addition, we also investigated the effect of the electrical stimulation of the M1 on chronic neuropathic pain condition in laboratory animals. Methods: Male Wistar rats were used. An adapted model of peripheral mononeuropathy induced by CCI was carried out by placing a single loose ligature around the right sciatic nerve. The acetone test was used to evaluate the cold allodynia in CCI or Sham (without ligature) rats. The MCS (M1) was performed at low-frequency (20 μA, 100 Hz) during 15 s by deep brain stimulation (DBS-Thomas Recording device) 21 days after CCI or Sham procedures. The cold allodynia was measured before and immediately after the neurostimulation of M1 in the following time-window: 0, 15 and 30 min after MCS. Results: Cold allodynia threshold increased in animals with chronic neuropathic pain submitted to the acetone test 21 days after the CCI surgery. The M1-stimulation by DBS procedure decreased the cold allodynia immediately and until 30 min after M1-stimulation in rats with chronic neuropathic pain. Conclusion: The current proposal for a CCI model by a single loose ligature of the sciatic nerve can be employed as an experimental model of chronic neuropathic pain in rats submitted to peripheral nervous system injury. The M1-stimulation produced antinociception in rats with chronic neuropathic pain. Thus, we reinforced that the MCS decreases cold allodynia in laboratory animals submitted to persistent sciatic nerve constriction and can be a more reasonable procedure for the treatment of chronic intractable neuropathic pain.

The present study evaluates whether the injection of serotonin, acetylcholine, glutamate, bradykinin, histamine, or substance P (SP) into the Zusanli (Stomach 36, ST 36) acupoint can also produce the acupuncture-induced antinociceptive effect on inflammatory or neuropathic pain. In this in vivo experimental study, a total of 450 male Swiss mice were used. Mice were injected with saline or complete Freund's adjuvant (CFA) or subjected to sham or chronic constriction injury (CCI) surgery. After the establishment of the inflammatory (4 hours) or the neuropathic pain (3 days), the animals (n = 6) received manual acupuncture, sham acupuncture, or injection of saline, serotonin, acetylcholine, glutamate, bradykinin, histamine, or SP into the ST 36 and were evaluated for up to 24 hours. Mechanical threshold was evaluated, and the L4-L6 dorsal root ganglion was used for analysis of the transient receptor potential vanilloid type 1 overexpression. The mice from both the CFA and CCI models treated with manual acupuncture had significant increases in the thresholds for more than 24 hours. Sham acupuncture stimulation did not change the thresholds. In the mice injected with each of the mediators, the thresholds were significantly increased for all times in both the CFA and CCI models. Transient receptor potential vanilloid type 1 overexpression in CFA and CCI mice was reduced at all times by injection of serotonin, acetylcholine, or SP but not by injection of glutamate, histamine, or bradykinin. Our data suggest that the neuroactive mediators released by acupuncture-induced tissue injury may contribute to acupuncture-induced analgesia. Keywords: acupuncture-induced analgesia, inflammatory pain, neuroactive mediators, neuropathic pain

Here in, we report the preparation and evaluation of four 3-hydroxy-piperidine-N-benzyl-aryl-acylhydrazone derivatives (6a–d) for their potential antinociceptive activity. In the tail flick test, compounds 6a and 6d exhibited a significant increase in the latency time of the animals, in comparison to the control group. These two compounds also showed a significant increase in the nociceptive threshold from 1 to 6 h after treatment in the CCI neuropathic pain model. In both cases, the antinociceptive activity was blocked by naloxone, suggesting an opioid mechanism of action, but without sedative or motor coordination effects.

Low-level laser therapy (LLLT) is the direct application of light to stimulate cell responses (photobiomodulation) to promote tissue healing, reduce inflammation, and induce analgesia; the molecular basis for these effects of LLLT remains unclear. The objective of this study was to evaluate the analgesic effect of LLLT in the rat plantar incision model of postoperative pain as well as to investigate some of the possible mechanisms involved in this effect. Wistar rats were submitted to plantar incision and treated with LLLT (830 nm, continuous-mode, 30 mW/cm2, 1–12 J/cm2). Postoperative thermal and mechanical hypersensitivity were monitored for 24 hours post-incision. In addition, the animals were pretreated with saline, naloxone (a nonselective opioid receptor antagonist; 20 µg/5 µl) or methysergide (5-HT2C, 5-HT2A, 5-HT7, 5-HT5a, 5-HT6, and 5-HT1F receptors antagonist; 30 µg/5 µl). Moreover, 24 hours after incision and treatment, the TNF-α and IL-1β levels in serum were evaluated. Our results demonstrate, for the first time, that LLLT at 3 or 8 J/cm2, but not at 1–2, 4–7, or 9–12 J/cm2, induced an analgesic effect on postoperative pain. Naloxone, but not methysergide, blocked the LLLT-induced anti-nociceptive effect. Additionally, IL-1-β and TNF-α production significantly decreased after LLLT at 3 or 8 J/cm2. Our results suggest that LLLT at 3 or 8 J/cm2 primarily modulates the endogenous opioids system and is not directly mediated by serotonergic receptors. Reduction of IL-1β and TNF-α may play a role in the antinociceptive action of LLLT. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.

Introduction: Photobiomodulation (PBM) assists in the processes of angiogenesis and cellular mitosis after skin lesion, contributing to tissue repair. Objective: to investigate the effects of photobiomodulation (during the proliferative phase) of 658 nm, 830 nm and 904 nm in the repair of skin lesions in an animal model. Method: 658 nm (G658), 830 nm (G830), 904 nm (G904) PBM, and control group (CG) integrated the research. We submitted the animals to an excisional wound and treatment at different wavelengths for 14 days. On the seventh and 14-1485004059th postoperative days, we calculated the area and percentage of lesion contraction. The animals were sacrificed on the 14-1485004056th postoperative day and cutaneous section of the injured region was collected for histomorphometric evaluation of the cellularity, neovascularization, thickness of the epidermis and volume density of collagen fibers colored with H&E and Picross Sirius respectively. For the statistical analysis, we applied the ANOVA test. Results: the G658 presented higher cellularity than GC (p = 0.03). The animals in the G658 group showed a significant increase in the neovascularization in relation to the CG (p = 0.01). Type III collagen significantly increased in G904 compared to G830 (p < 0.0001) and CG (p < 0.0001). The G658 had a significant increase in type III collagen fibers compared to G830 (p < 0.0001) and GC (p < 0.0001). We found no significant difference in the thickness of the epidermis, wound area, and in the percentage wound of contraction between the analyzed groups. Conclusion: PBM was effective to stimulate the tissue repair process, with better results for the 658 nm wavelength.

Introduction Injuries and/or dysfunctions in the somatosensory system can lead to neuropathic pain. Transient receptor potential vanilloid sub‑type 1 (TRPV1) play an important role in the development of allodynia and hyperalgesia following injury and the ensuing inflammatory conditions. Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 agonist and many different administration routes are available for different mechanisms and different effects. RTX is used intraperitonially as a model of neuropathic pain or epidurally and topically to produce prolonged analgesic effects. However, the use of RTX is controversial because its neurotoxicity and margin of safety have not been addressed adequately. The present study evaluates the effect of intrathecal RTX on the induction and allodynia behavior of animals submitted to neuropathic pain by chronic constriction injury (CCI). Methods 160 Swiss mice were randomly distributed into two groups: intrathecal pre‑treatment group (PRE) aiming the effect in induction of allodynia and late intrathecal treatment group (POST) to evaluate the antiallodynic effect of the RTX on mechanical nociceptive threshold evaluated by the Von Frey hair filaments. Additionally, we evaluated the expression of TRPV1 in dorsal root ganglia (DRG) by western blotting after PRE‑ and POST‑treatment with RTX. Results Our results showed that the CCI mice developed prolonged mechanical allodynia‑like behavior in ipsilateral paw after surgery up to 24 hours. The PRE‑ and POST‑treatment groups presented significant antiallodynic effects in ipsilateral paw for 24 hours. Only the POST‑treatment group showed a significant reduction of expression of the TRPV1 receptor after CCI. Conclusion The presented data demonstrated that both PRE‑ and POST‑treatment with RTX given intrathecally produced potent antiallodynic activities in CCI mice and that POST‑treatment can reduce TRPV1 expression in DRG, suggesting that POST‑treatment RTX can revert central sensitization and its associated allodynia.

Preemptive analgesia involves introducing an analgesic before noxious stimulation. Electroacupuncture (EA) activates descending mechanisms that modulate nociceptive inputs into the spinal dorsal horn. This study evaluated whether preoperative EA is more effective than postoperative EA in reducing incision pain in rats. The nociceptive threshold to mechanical stimulation was utilized to examine the effects of an intraperitoneal injection of saline (0.1 mL/kg) or naloxone (1 mg/kg) on antinociception induced by a 20-minute period of 2-Hz or 100-Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints before surgical incision, or 10 minutes after or 100 minutes after surgical incision of the hind paw. The extent of mechanical hyperalgesia after the incision was significantly attenuated by the application of 100-Hz EA preoperatively, but not by its application at 10 minutes or 100 minutes postoperatively. By contrast, 2-Hz EA was effective against postoperative hyperalgesia when applied 10 minutes or 100 minutes after surgery but not when it was applied preoperatively. Only the effect of 2-Hz EA applied 10 minutes after surgery was sensitive to naloxone. The present study showed for the first time that 100-Hz EA, but not 2-Hz EA, exerts a nonopioidergic preemptive effect against postincision pain in rats.

The objective of this study was to compare the effects of one or multiple sessions of electroacupuncture (EA) in patients with chronic low back pain. The outcome measures were visual analog score (VAS), pressure pain threshold (PPT), McGill pain questionnaire (MPQ), Roland Morris disability questionnaire (RMDQ), low back skin temperature, surface electromyography of longissimus muscle (contraction/rest) and blood cytokines. After examination (AV0), patients were submitted to EA (2 Hz, 30 minutes, bilaterally at the SP6, BL23, BL31, BL32, BL33, and BL60) and were revaluated after one week (AV1). Patients with VAS 3 (VAS >3 group, n = 20) were submitted to one weekly EA-treatment and revaluated after three weeks (AV2). The VAS 3 group showed reduction in VAS and increased PPT in AV1 and a reduction in MPQ and RMDQ only in AV2. No significant differences were found in electromyography, temperature or cytokines. Thus, despite 2Hz-EA is effective reducing low back pain, some patients only experienced reduced pain intensity and improved functional capacity after full treatment. Keywords: disability, electroacupuncture, low back pain, pain threshold

Although transcutaneous electrical nerve stimulation (TENS) has been proposed to modulate pain and the mechanisms underlying analgesia remain poorly understood, evidence of anti-inflammatory effect is more limited. The purpose of this study was to examine the opioidergic mechanisms of TENS effects in two different frequencies on pain and inflammatory edema in the ankle sprain model in rats. Threshold to mechanical stimulation was utilized to examine the changes produced by intraperitoneal injection of non-selective opioid antagonist naloxone on the antihyperalgesic effect induced by a 20-min period of 2Hz or 100Hz TENS in the ankle sprain model, produced by manually overextending the lateral ligaments. Ankle sprain induced a long-lasting reduction in paw withdrawn latency (PWL) after 30 minutes for up to 24 hours in sham TENS (SH-TENS) treated rats. The reduced PWL after the induction of ankle sprain was restored partially at 0,1,2,3 and 6, but not 24 hours, after the termination of 2 Hz-TENS (LF-TENS). In 100Hz (HF-TENS) the reduction in PWL was shorter than LF-TENS and both LF and HF effects were fully blocked in naloxone-treated rats. LF- and HF-TENS treated rats did not reach the elevation of edema and presented a progressive edema reduction for over 24 hours when compared to SH-TENS group. Both effects were reduced by naloxone. TENS-induced antihyperalgesic and anti-edematous effects observed in ankle sprain model were mediated by the endogenous opioid system. RESUMO Embora estimulação elétrica nervosa transcutânea (TENS) tem sido proposta para modular a dor e os mecanismos subjacentes a analgesia permanecem mal compreendidos, evidências do efeito anti-inflamatório são mais limitadas. O objetivo deste estudo foi examinar os mecanismos opioidérgicos de efeitos de TENS em duas frequências diferentes sobre dor e edema inflamatório no modelo de entorse de tornozelo em ratos. Limiar de estimulação mecânica foi utilizado para examinar as alterações produzidas pela injeção intraperitoneal de naloxona, um antagonista opioide não-seletivo, sobre o efeito anti-hiperalgésico induzido por um período de 20 min de 2Hz ou 100Hz de TENS no modelo de entorse de tornozelo, produzido ultrapassando manualmente os ligamentos laterais. Entorse de tornozelo induziu uma redução duradoura na latência de retirada da pata (PWL) depois de 30 minutos até 24 horas em ratos tratados para TENS “simulada” (SH-TENS). A PWL reduzida após a indução de entorse de tornozelo foi restaurada parcialmente em 0,1,2,3 e 6, mas não em 24 horas, após o término do 2 Hz-TENS (LF-TENS). Em 100Hz (HF-TENS) a redução de PWL foi menor do que LF-TENS e tanto os efeitos HF e LF foram totalmente bloqueados em ratos tratados com naloxona. Ratos tratados com LF- e HF-TENS não alcançou a elevação do edema e apresentaram uma redução progressiva do edema por mais de 24 horas, quando comparado ao grupo SH-TENS. Ambos os efeitos foram reduzidos pela naloxona. Efeitos anti-hiperalgésicos induzidos por TENS e efeitos antiedematosos observados no modelo de entorse de tornozelo foram mediados pelo sistema de opioides endógenos. RESUMEN Aunque la estimulación nerviosa eléctrica transcutánea (TENS) ha sido propuesta para modular el dolor y los mecanismos subyacentes a la analgesia sigue siendo mal entendida, la evidencia del efecto antiinflamatorio es limitada. El propósito de este estudio fue examinar los mecanismos opioidérgicos de los efectos de la TENS en dos frecuencias diferentes sobre el dolor y el edema inflamatorio en un modelo de ratas con esguince de tobillo. Se utilizó el umbral a la estimulación mecánica para examinar los cambios producidos por inyección intraperitoneal del antagonista opiáceo no selectivo naloxona sobre el efecto antihiperalgésico inducido por un período de 20 minutos de 2Hz o 100Hz TENS en el modelo con esguince de tobillo, producido por sobrecarga manual de los ligamentos laterales. El esguince de tobillo indujo una reducción de larga duración en latencia de la pata retraída (PWL) después de 30 minutos por hasta 24 horas en simulación de la TENS (SH-TENS) para las ratas tratadas. El PWL reducido después de la inducción del esguince de tobillo fue restaurado parcialmente en 0,1,2,3 y 6, pero no por 24 horas, después de la terminación de 2 Hz-TENS (LF-TENS). La reducción en PWL fue menor que LF-TENS en 100Hz (HF-TENS) y tanto los efectos de LF como de HF fueron completamente bloqueados en ratas tratadas con naloxona. Las ratas tratadas con LF- y HF-TENS no alcanzaron la elevación del edema y presentaron una reducción progresiva del edema durante más de 24 horas en comparación con el grupo SH-TENS. Ambos efectos fueron reducidos por la naloxona. Efectos antihiperalgésicos y antiedematosos TENS-inducidos observados en el modelo con esguince de tobillo fueron mediados por el sistema opioide endógeno.