The journal of pain : official journal of the American Pain Society
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Retraction Of Publication
Perioperative perineural infusion of bupivacaine and clonidine following lower extremity amputation.
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This is a longitudinal predictive study to examine gender differences in the clinical correlates of risk for opioid misuse among chronic pain patients prescribed opioids for pain. Two hundred seventy-five male and 335 female patients prescribed opioids for chronic noncancer pain were asked to complete a series of baseline questionnaires, including the revised Screener and Opioid Assessment for Pain Patients (SOAPP-R). After 5 months, the subjects were administered a structured prescription drug use interview (Prescription Drug Use Questionnaire; PDUQ) and submitted a urine sample for toxicology assessment. Their treating physicians also completed a substance misuse behavior checklist (Prescription Opioid Therapy Questionnaire; POTQ). At 5-month follow-up, women showed higher scores on the PDUQ (P < .05), whereas men had a higher incidence of physician-rated aberrant drug behavior on the POTQ (P < .05). An item analysis of the SOAPP-R, PDUQ, and POTQ showed that women tended to score higher on items relating to psychological distress, whereas the male patients tended to report having more legal and behavioral problems. These results suggest that risk factors associated with prescription opioid misuse may differ between men and women. ⋯ Understanding gender differences in substance abuse risk among chronic pain patients is important for clinical assessment and treatment. This study suggests that women are at greater risk to misuse opioids because of emotional issues and affective distress, whereas men tend to misuse opioids because of legal and problematic behavioral issues.
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Previous studies have demonstrated that sex differences in pain responsivity can be detected using various models of experimentally induced pain. The present study employed the mechanical pressure test in order to examine potential differences in pain report among men, normally menstruating women (NMW), and women taking monophasic oral contraceptives (OCW). Testing occurred during 5 phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) and all participants completed 10 sessions (2 sessions per phase). Menstrual-cycle phase was estimated for OCW based on their first day of menses. Men were tested at time points that roughly corresponded to the intervals during which the different phases occurred in NMW. During the mechanical pressure test, 4 different weights were placed on the fingers, one at a time, and ratings of pain were recorded for 30 seconds. The statistical decision-making model and a forced-choice procedure were used to analyze the response data. Two variables, based on signal detection theory, were thus generated: P(A), a measure of sensory pain, and B, a measure of response bias. P(A) is believed to be a measure of pain sensitivity while B measures stoicism. NMW tended to report lower P(A) values, indicating reduced ability to discriminate among different stimulus intensities, during the menstrual and late luteal phases compared to the luteal phase. OCW reported lower B values, indicating less stoicism, during the menstrual compared to the follicular and ovulatory phases. Men tended to have significantly lower B values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle effects in NMW and OCW. Sex differences were few, with more group differences and trends emerging between OCW and men, as opposed to men and NMW. ⋯ The lack of consistent differences between men and NMW underscores the subtle impact of sex and hormonal changes in pain report. In addition, the data obtained in NMW support the notion that changes in hormone levels during the menstrual cycle can lead to changes in pain responsivity as NMW had trends for better discrimination in menstrual phases when estradiol levels were highest.
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Repeated injections of acidic saline into the gastrocnemius muscle induce both muscle and cutaneous hypersensitivity. We have previously shown that microinjection of local anesthetic into either the rostral ventromedial medulla (RVM) or the nucleus reticularis gigantocellularis (NGC) reverses this muscle and cutaneous hypersensitivity. Although prior studies show that NMDA receptors in the RVM play a clear role in mediating visceral and inflammatory hypersensitivity, the role of NMDA receptors in the NGC or in noninflammatory muscle pain is unclear. Therefore, the present study evaluated involvement of the NMDA receptors in the RVM and NGC in muscle and cutaneous hypersensitivity induced by repeated intramuscular injections of acidic saline. Repeated intramuscular injections of acidic saline, 5 days apart, resulted in a bilateral decrease in the withdrawal thresholds of the paw and muscle in all groups 24 hours after the second injection. Microinjection of NMDA receptor antagonists into the RVM reversed both the muscle and cutaneous hypersensitivity. However, microinjection of NMDA receptor antagonists into the NGC only reversed cutaneous but not muscle hypersensitivity. These results suggest that NMDA receptors in the RVM mediate both muscle and cutaneous hypersensitivity, but those in the NGC mediate only cutaneous hypersensitivity after muscle insult. ⋯ The current study shows that NMDA receptors in supraspinal facilitatory sites maintain noninflammatory muscle pain. Clinical studies in people with chronic widespread, noninflammatory pain, similarly, show alterations in central excitability. Thus, understanding mechanisms in an animal model could lead to improved treatment for patients with chronic muscle pain.
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Intraplantar injection of bee venom (BV) produces persistent spontaneous nociception (PSN), hyperalgesia, and inflammatory swelling of the injected paw. The present study was designed to determine the roles of peripheral metabotropic glutamate receptors (mGluRs) in BV-induced nociception and inflammation. We determined the effects of the group I mGluR antagonist AIDA, the group II mGluR agonist ADPC, and the group III mGluR agonist L-AP4 on BV-induced PSN, mechanical hyperalgesia, and inflammatory swelling. Pretreatment with intraplantar injections of AIDA, ADPC or L-AP4 at different doses significantly inhibited BV-induced PSN over the 1-hour observational period. The inhibitory effects of ADPC and L-AP4 were completely abolished by pretreatment with the group II mGluR antagonist LY341495 and the group III mGluR antagonist MSOP, respectively. Pretreatment with ADPC prevented the BV-induced decrease in paw-withdrawal mechanical threshold (PWMT) in a dose-dependent manner, while pretreatment with AIDA or L-AP4 had no effect. The antihyperalgesic effect of ADPC was completely abolished by pretreatment with LY341495. Pretreatment with AIDA, ADPC or L-AP4 at different doses had no effect on the BV-induced increase in the paw volume (PV), a measurement of inflammatory swelling. All contralateral drug treatments at the highest doses had no effect on BV-induced PSN, decreases in PWMT or increases in PV, eliminating the possibility of drug-induced systemic effects. These data suggest that the activation of mGluRs in the periphery may play a differential role in BV-induced nociception and inflammation. ⋯ The present study demonstrated that the intraplantar injection of antagonists or agonists of different mGluRs produced differential effects on bee venom-induced persistent spontaneous nociception and mechanical hyperalgesia. However, no effects on inflammation were observed, suggesting that mGluRs in the periphery have differential roles. Thus, therapies specifically targeting metabotropic glutamate receptors may improve the treatment of patients with persistent spontaneous nociception and hyperalgesia.