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There is still controversy surrounding the use of opioid medication for patients with chronic nonmalignant pain. Schofferman has argued that long-term opioid use leads to a "downhill spiral" associated with loss of functional capacity and a corresponding increase in depressed mood. The present study was a retrospective comparison of opioid users vs. non-users to determine whether: (a) users have higher levels of disability, medical visitation, depression, and pain; (b) the behavioral problems associated with opioid use persist after controlling for the influence of other medication; (c) opioid use is in fact a predictor of illness behavior; and (d) higher levels of opioid consumption are associated with higher levels of disability and depression. A consecutive series of 243 patients with nonmalignant pain about to enroll at a tertiary clinic were retrospectively assigned to either an Opioid User (n = 87) or Non-User (n = 156) group. Compared to Non-Users, Opioid Users were more likely to be physically disabled ( P

UNLABELLED The calcium channel blocker nifedipine has analgesic properties that are enhanced by nicotine. Although it is not known how this analgesic state might affect the awareness of anginal pain and impending myocardial infraction, recent studies have shown an increased mortality associated with the use of large doses of nifedipine. Because both nifedipine- and nicotine-induced analgesia involve serotonergic mechanisms, we studied the effects of the serotonin biosynthesis inhibitor parachlorophenylalanine (pCPA) on nifedipine- and nicotine-induced analgesia. Nociception was assessed by tail-flick method. Rats pretreated with pCPA (300 mg/kg intraperitoneally [IP]) followed by either nifedipine (15 mg/kg IP) or nicotine (1 mg/kg subcutaneously) had a increase in tail-flick latency of 41% (P = 0.09) and 50% (P = 0.05), respectively, compared with animals that did not receive pCPA. Additionally, rats pretreated with pCPA followed by a combination of nicotine and nifedipine doubled their tail-flick latency (P = 0.0001) compared with animals that were not treated with pCPA. These data further support the involvement of the serotonergic system in both nifedipine- and nicotine-induced analgesia and suggest that drugs that affect serotonin levels, including tricyclic antidepressants and serotonin-specific reuptake inhibitors, may also affect the analgesia induced by nifedipine and nicotine. IMPLICATIONS This study examines the effect of serotonin depletion on nicotine- and nifedipine-induced analgesia. Nifidipine is a calcium channel blocker used to treat high blood pressure. It also has pain-relieving properties that are enhanced by nicotine. Because both nifedipine- and nicotine-induced analgesia involve the neurotransmitter serotonin, it is important to know how changes in serotonin concentration might affect both nicotine- and nifedipine-induced analgesia. This study not only supports the involvement of the serotonergic system in both nifidipine- and nicotine-induced analgesia, but also suggests that drugs that affect serotonin levels may also affect analgesia induced by nifidipine and nicotine.

The purpose of this study was to determine whether ondansetron (OND) has local anesthetic effects. Using a patch-clamp technique, we showed that OND concentration dependently blocked Na channel currents in freshly isolated neurons of rat brains with a 50% inhibition concentration of 12 microM. The blockade started immediately when OND was applied to the cell body using a fast perfusion system, reached a plateau within 15 s, and recovered to the control level within 30 s after washout of the OND-containing solution. Because this is a known property of local anesthetics, we used the tail-flick technique to verify this effect in vivo in Sprague-Dawley rats (n = 46). OND was injected subcutaneously into the tail at the doses of 0.08, 0.16, and 0.2 mg. The tail-flick latency increased 2 min after OND injection, reaching the plateau within 5 min. This effect was dose-related, lasting from 10 to 25 min. These preliminary data indicate that OND, a selective 5-HT3 receptor antagonist, might serve as a prototype molecule for development of a novel series of local anesthetics.Ondansetron is a drug used to prevent vomiting, especially in cancer patients after chemotherapy. We found that it also causes numbness when injected under the skin. This new action may contribute to its role in "calming the stomach." We studied the effect of ondansetron on the isolated brain cells of live rats.

Patients with reflex sympathetic dystrophy (RSD) often present with pain and disability that cannot be explained on the basis of objective physical findings. This has led some to speculate that RSD may be caused or mediated by non-organic factors. Unfortunately, there have been few studies using standardized measures of mood and illness behavior that have compared patients with RSD to patients with other chronic pain disorders. The goal of the present study, therefore, was to compare the pattern of psychological dysfunction in patients with RSD to the pattern of dysfunction in patients with chronic back pain and local neuropathic pain. Patients with back pain resemble those with RSD in that both may report symptoms that cannot be reconciled with objective physical findings. Patients with local neuropathy, by contrast, report pain that is both circumscribed and consistent with a known organic cause. The records of 253 patients attending a tertiary pain service were retrospectively reviewed and three distinct (non-overlapping) diagnostic groups were formed: 25 were assigned to the RSD group; 44 to the back pain group; and 21 to the local neuropathy group. Using a set of stringent criteria to diagnose RSD and an analysis of covariance to control for differences in symptom duration and age, the present study found no evidence to suggest that patients with RSD were psychologically unique. Instead, RSD patients were remarkably similar to those with local neuropathy in terms of their symptom reporting, illness behavior, and psychological distress. The only exception was that RSD patients had more disability days during the preceding 6 months than those with local neuropathy (P < 0.05). The back pain group, on the other hand, presented with more diffuse pain complaints (P < 0.05) and had a greater number of non-specific medical symptoms (P < 0.05) compared to either the RSD or local neuropathy group. In contrast to previous research using less stringent diagnostic criteria, there was no evidence of higher pain scores or lower levels of psychological distress among patients with RSD. In addition, a validated survey of childhood trauma found that sexual abuse, physical abuse, emotional abuse, and cumulative trauma were evenly distributed among all three diagnostic groups. The burden of proof would appear to be upon those who advocate the non-organic hypothesis to provide credible evidence of psychological involvement in the etiology of RSD.

Antinociceptive effect of nifedipine (15 mg/kg i.p.) and verapamil (10 mg/kg s.c.) was examined in rats chronically exposed to nicotine (6 mg/kg/day via Alzet osmotic pump for 28 days) and after nicotine withdrawal. Sham operated rats served as control for testing DMSO (dimethylsulfoxide, a solvent for nifedipine), nifedipine and verapamil alone. Nociception was measured by the tail-flick technique. Nifedipine, but not verapamil, injected to control rats produced a ceiling tail-flick latency (20 sec) 30 min after the injection, lasting for 10 min. In rats exposed to chronic nicotine for 3 days, nifedipine treatment exhibited ceiling tail-flick latency within 10 min lasting for 80 min. Tested in rats exposed to nicotine for 3 weeks, nifedipine treatment produced this effect 25 min after the injection lasting for 60 min. Nicotine withdrawal abolished this effect. Verapamil did not exhibit any significant changes in tail-flick latencies. These data support our hypothesis that smoking patients treated with nifedipine could be at a potential risk in developing a high pain threshold and missing the first sign of heart attack -a chest pain.

We examined the modulatory effect of nifedipine (NIF, 0.04, 2, 5 and 15 mg/kg i.p.) and verapamil (VER, 2.5 and 10 mg/kg s.c.) on nicotine-induced antinociception in male rats, employing the tail-flick (TF) test. All rats were divided according to their responses to nicotine (1 mg/kg s.c.) alone, and classified as responders and nonresponders; both types were used. Both tested drugs were injected simultaneously with nicotine (NIC). In responders , NIC (1 mg/kg s.c.) alone produced a ceiling TF latency (15 sec) within 2.5 in lasting for 2.5 – 7.5 min. NIF, at the dose of 15 mg/kg i.p., prolonged this effect up to 40–50 min. Lower doses (5, 2 and 0.04 mg/kg) were not effective. VER in either dose did not prolong NIC-induced antinociception. In nonresponders , NIF also potentiated NIC-induced antinociception, and this effect appeared to be dose-related, lasting from 10 up to 40 min. VER was ineffective in either dose. These data support our hypothesis that calcium is involved, at least in part, in nicotine-induced antinociception. The potential risk for smoking patients treated with NIF is discussed.

The serotonergic system is involved in pain transmission and the 5-hydroxytryptamine (5-HT3) receptor subtype mediates some of these effects at the spinal level. Therefore, we explored the effects of the serotonergic system on nifedipine-induced analgesia by using the 5-HT3 receptor antagonist ondansetron. Male Sprague-Dawley rats were pretreated with ondansetron (1 mg/ kg intraperitoneally) or normal saline. After 15 min, rats received injections of nifedipine (15 mg/kg intraperitoneally) or dimethylsulfoxide (DMSO), solvent for nifedipine, as a control. Nociception was assessed by tail-flick method. Rats treated with nifedipine alone had an increase in tail-flick latency of 122%, as measured by the area under the curve, compared to rats treated with DMSO alone. Pretreatment with ondansetron, however completely blocked the analgesic effect of nifedipine, with tail-flick latency remaining at baseline throughout the measurement period. These results indicate that the 5-HT3 receptor plays an important role in the analgesic response to nifedipine and that medications that block this receptor may decrease the analgesic effectiveness of this type of therapy.

Acupuncture is an easily practiced and effective therapy for the prevention and treatment of various diseases, through the use of needles stimulating the human body by trained practitioners with special manipulating skills, based on theories of“meridian” and “acupoint” of Traditional Chinese Medicine (TCM). In clinical practice, acupuncturists proceed as follows: first a precise diagnosis is made based on an overall analysis of the signs and syndromes of patients, and then, appropriate acupoints of “channels” are chosen for stimulation by needling methods using established therapeutic principles.

We explored the analgesic effect of epidural nifedipine in male Sprague-Dawley rats. By using an implanted epidural catheter, the rats were given 35 microL of dimethylsulfoxide (DMSO) alone or DMSO containing 2.5, 5, 10, or 20 microM of nifedipine. Analgesia was measured by tailflick (TF) involving spinal reflexes, and by hotplate (HP) requiring an intact central nervous system. The latencies were recorded up to 120 min after the injection. The cutoff time of the noxious stimuli was 20 s in the TF and 60 s in the HP to prevent tissue damage. The TF technique revealed a significant difference from the control at doses of 5, 10, and 20 microM with no difference among the groups. Maximum latencies (cutoff time) lasted for 15, 30, and 40 min at doses of 5, 10, and 20 microM, respectively. The HP technique disclosed a dual effect: a significant decrease at the dose of 2.5 microM, no effect at 5 microM, and an increase at 10 and 20 microM. However, the median latency did not reach the cutoff time. We conclude that nifedipine, given epidurally, possesses antinociceptive properties at the dose of 5 microM and higher, detected better by the TF than HP. Our data suggest that the antinociceptive effect of nifedipine, at the studied doses, is more prominent at the spinal than the supraspinal level.

To gain further insight into the mechanism of cell photostimulation by laser light ((lambda) equals 632.8 nm), DNA synthesis was measured in the human neuroblastoma cell line BE(2)-C. Cells were irradiated at high density to establish the characteristics of cellular energy into S- phase in response to laser stimulation. BE(2)-C cells after release from a quiescent, growth arrested state exhibited increased incorporation of isotope 12 hours after replating at subconfluent density in the presence of 2.5% fetal bovine serum (FBS) and [3H] thymidine. In contrast, cells replated under the same conditions, but stimulated with 15% FBS exhibited a time lag of approximately 16 hours in apparent DNA synthesis. These results were not corroborated by flow cytometry. Laser irradiation did not affect the fraction of cells entering S-phase. It therefore appears that the stimulatory effect of He-Ne laser irradiation on BE(2)-C cells is to enhance DNA synthesis while not altering the G1-S transition rate.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant antinociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 microM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotine alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl2 (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.)--induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl2 completely abolishes, nicotine-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect.

Nicotine (6 mg/kg/day) was administered subcutaneously via Alzet osmotic pumps to rats for 28 days. Nociception was measured by the hot-plate and tail-flick methods. A significant antinociceptive effect was demonstrated during the first week of the treatment; after that tolerance developed, lasting for the remaining period of nicotine treatment. This effect was more pronounced in the habituated, rather than in the naive, rats. Rats subjected to nicotine withdrawal tended to exhibit the nociceptive effect for 10 days with an overall P value on the border of significance. This chronic nicotine-induced antinociception and nicotine withdrawal-induced nociception was detectable only by hot-plate but not the tail-flick technique.

A patient with intractable abdominal pain due to chronic pancreatitis was successfully treated by direct electrical stimulation of the celiac plexus. The details of the procedure are presented. This simple innocuous technique could be of value in treating patients with pain due to chronic pancreatitis who would otherwise have a near normal life expectancy. Also, it can be used in patients suffering from cancer of the pancreas and upper abdominal viscera.

The authors determined cardiovascular, renal, and hormonal responses to increased airway pressure during continuous positive-pressure ventilation (CPPV) and continuous positive airway pressure (CPAP). Nine healthy, hydrated laboratory swine had appropriate catheters placed to allow for measurement of intrapleural, aortic, inferior vena caval, and left ventricular end-diastolic pressures; cardiac output; and urinary flow. Samples of arterial blood were analyzed for oxygen and carbon dioxide tensions, pH, plasma vasopressin, osmolality, and creatinine and sodium concentrations. Urine was analyzed for osmolality and creatinine and sodium concentrations, and volume was recorded. Intrapleural pressure was subtracted from left ventricular end-diastolic pressure to calculate transmural pressure, a reflection of left ventricular filling pressure. Glomerular filtration rate and urinary free-water and osmolal clearances were also calculated. Expiratory left ventricular filling pressure was decreased equally by CPAP and CPPV. However, inspiratory left ventricular filling pressure and cardiac output were decreased by CPPV only. Urinary flow and glomerular filtration rate were decreased equally by CPAP and CPPV. Sodium excretion was decreased and plasma vasopressin increased by CPPV, but not by CPAP. Urinary free water and osmolal clearances were not changed by either ventilatory pattern. Although many of the renal-function variables were affected similarly by CPPV and CPAP, these alterations were not influenced solely by cardiac output or vasopressin, because only CPPV depressed cardiac output and increased vasopressin levels.

A new double-needle technique for brachial plexus block via the axillary route has been used in 30 patients. The results have been evaluated against those of a control group in which the classic method for the block was used. Simplicity in performance, high success rate, and a reduced chance of traumatizing the neurovascular tissue stand out as advantages of the new technique.

Laser photobiostimulation (LPBS) at the pulsing frequency of 4 Hz applied to the low resistance point located at the base of the tail of the rat, (Governing Vessel Meridian 1), produced a hypoalgesic effect, measured by tail-flick and hot-plate techniques. Pre-treatment with low dose naloxone (2 mg/kg) did not reverse the hypoalgesic effect of LPBS. High dose naloxone (20 mg/kg) reversed only partially, but significantly, the hypoalgesic effect of LPBS measured by hot-plate, but not that measured by the tail-flick technique. These data suggest that mechanisms other than endogenous opioids may be involved in LPBS-induced hypoalgesia.

Plasma vasopressin (VP), serum and urine osmolality (Sosm, Uosm), serum and urine electrolytes (Na+, K+), cardiac index, and arterial pressure were studied before, during, and after cardiopulmonary bypass (CPB) in 27 patients. Of these, 13 underwent coronary artery bypass (CAB), seven underwent aortic valve replacement (AVR), and seven underwent mitral valve replacement (MVR). During CPB, plasma VP concentration rose significantly in all three groups. The CAB group showed the highest average increase in plasma VP concentration during CPB over the preinduction values, an increase significantly higher than that in the valve groups (p

We demonstrated a 50% increase in pain threshold following laser photobiostimulation (LPBS), employing rat tail-flick test. Helium-neon laser (1 mW) of three different pulsing frequencies (4, 60, and 200 Hz) was applied on tail low resistance point for 15 seconds and tail-flick latencies were measured 30 minutes, 1 hour, 24 hours, 48 hours and 7 days later. LPBS of 4 Hz produced hypoalgesia of rapid onset and short duration while the response to 60 Hz was delayed and lasted longer. LPBS of 200 Hz did not produce any hypoalgesia.

We studied the effect of aging on the decline in vasopressin (VP) release from the rat neurohypophyses (NH) as evoked by repeated stimuli with high K+ (56 mM) Locke's solution in vitro. Isolated NHs, without pars intermedia, of 2-, 12- and 30-month-old male Fisher 344 rats arbitrarily labeled as young, adult, and old were individually superfused with synthetic medium TC 199. Following the initial traumatic release, the glands were stimulated three times for 10 min each with recovery periods of 35 min between stimulations. VP was measured by radioimmunoassay. Expressed per mg NH, basal VP release in the old rats, and stimulated VP release in both the adult and old rats, was decreased. The gradual decline (slope) of VP release following subsequent stimuli with high K+ was proportional, however, in all age groups. Thus, decreasing response of VP release to repeated stimulation is a function of the initial response but is not age related. These findings suggest that only some components of the chain of events involved in the release mechanisms are impaired in aging animals, whereas others may remain unaffected.

The effects of 46 h of mechanical ventilation and PEEP on urinary output, sodium excretion, and renal and cardiovascular function were examined. Dogs sedated with sodium pentobarbital were ventilated using one of three modes: spontaneous ventilation (SV), controlled mechanical ventilation (CMV), or CMV with 10 cmH2O positive end-expiratory pressure (CMV with PEEP). Intravenous fluids were given at a constant rate throughout the study and measurements of renal and cardiovascular function were made over four periods. Dogs whose lungs were ventilated with PEEP displayed more than two times the amount retention seen in the other groups as assessed by mean weight gain. This was due to an initial depression of urine flow, sodium excretion, and free water clearance. Urinary flow rate approximated the rate of fluid infusion by 20 h in SV dogs and by 27 h during CMV, while the maximum during CMV with PEEP occurred at 46 h. There were no significant differences in glomerular filtration rate, renal corticomedullary blood flow distribution, or renal blood flow between groups. During the 46 h, cardiac index increased (SV, +16%; CMV, +19%; CMV with PEEP, +64%), while systemic vascular resistance (SV, -28%; CMV, -30%; CMV with PEEP, -57%), renal vascular resistance (SV, -12%; CMV, -20%; CMV with PEEP, -23%), and mean arterial pressure (SV, -16%; CMV, -15%; CMV with PEEP, -15%) decreased in all groups. This study has demonstrated that when a constant sodium and water load was provided, the SV and CMV groups were rapidly able to adjust the urinary excretion to meet input, while the return of renal function toward normal in the CMV with PEEP group was delayed until almost 46 h from the start of ventilation.

TRANSIENT bacteremia following dental manipulation, 1 genitourinary instrumentation, 2 sigmoidoscopy, 3 bronchoscopy, 4 barium enema, 5 percutaneous liver biopsy, 6 tonsillectomy, and massage of such loci as infected boils and carbuncles 7 may produce bacterial endocarditis in patients with congenital or rheumatic heart disease. On the basis of these findings, the American Heart Association has recommended antimicrobial chemoprophylaxis for patients with cardiovascular abnormalities undergoing these procedures. This communication reports a prospective study showing that transient bacteremia with definable characteristics may follow nasotracheal suctioning (NTS). Methods Subjects.— Sixty-eight patients hospitalized for various reasons at the West Virginia University Medical Center intensive care unit (ICU) underwent NTS as ordered by their attending physicians. Thirty healthy medical students served as controls. The design and intent of the study was explained to each patient or member of the family. Culture Studies.— All subjects had nasopharyngeal cultures taken before they underwent NTS. The cultures were