The journal of pain : official journal of the American Pain Society
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The amygdala contributes to the generation of pain affect, and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study compared the contribution of N-methyl-d-aspartate (NMDA) receptor agonism and antagonism in the CeA to generation of the affective response of rats to an acute noxious stimulus. Vocalizations that occur following a brief tail shock (vocalization afterdischarges) are a validated rodent model of pain affect and were preferentially suppressed, in a dose-dependent manner, by bilateral injection into the CeA of NMDA (.1, .25, .5, or 1 μg/side) or the NMDA receptor antagonist d-(-)-2-amino-5-phosphopentanoic acid (AP5; 1, 2, or 4 μg/side). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of NMDA or AP5 into the CeA. Injection of NMDA, but not AP5, into the CeA increased c-Fos immunoreactivity in the ventrolateral periaqueductal gray, and unilateral injection of the μ-opiate receptor antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; .25 μg) into ventrolateral periaqueductal gray prevented the antinociception generated by injection of NMDA into the CeA. These findings demonstrate that although NMDA receptor agonism and antagonism in the CeA produce similar suppression of pain behaviors, they do so via different neurobiologic mechanisms. ⋯ The amygdala contributes to production of the emotional dimension of pain. NMDA receptor agonism and antagonism within the CeA suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders.
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Most clinically used opioids are mu-opioid receptor agonists. Therefore, genetic variation of the OPRM1 gene that encodes the mu-opioid receptor is of great interest for understanding pain management. A polymorphism 118A>G (rs1799971) within the OPRM1 gene results in a missense mutation and affects the function of the receptor. We studied the association between the 118A>G polymorphism and oxycodone analgesia and pain sensitivity in 1,000 women undergoing breast cancer surgery. Preoperatively, experimental cold and heat pain sensitivities were tested. Postoperative pain was assessed at rest and during motion. Intravenous oxycodone analgesia was titrated first by a research nurse and on the ward using a patient-controlled analgesia device. The primary endpoint was the amount of oxycodone needed for the first state of adequate analgesia. For each patient, the 118A>G polymorphism was genotyped using the Sequenom MassARRAY (Sequenom, San Diego, CA). The association between this variant and the pain phenotypes was tested using linear regression. The 118A>G variant was associated significantly with the amount of oxycodone requested for adequate analgesia (P = .003, β = .016). Collectively, oxycodone consumption was highest in individuals having the GG genotype (.16 mg/kg), lowest for those with the AA genotype (.12 mg/kg), and moderate for those having the AG genotype (.13 mg/kg). Furthermore, the G allele was associated with higher postoperative baseline pain ratings (P = .001, β = .44). No evidence of association with other pain phenotypes examined was observed. ⋯ This study demonstrates that the OPRM1 118A>G polymorphism was associated with the amount of oxycodone required in the immediate postoperative period. Although a significant factor for determining oxycodone requirement, the 118A>G polymorphism alone explained less than 1% of the variance. No association was found between 118A>G and experimental pain
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Ischemic myalgia is a unique type of muscle pain in the patient population. The role that discrete muscle afferent subpopulations play in the generation of pain during ischemic events, however, has yet to be determined. Using 2 brachial artery occlusion models to compare prolonged ischemia or transient ischemia with reperfusion of the muscles, we found that both injuries caused behavioral decrements in grip strength, as well as increased spontaneous pain behaviors. Using our ex vivo forepaw muscles, median and ulnar nerves, dorsal root ganglion, and spinal cord recording preparation, we found after both prolonged and transient ischemia that there was a significant increase in the number of afferents that responded to both noxious and non-noxious chemical (lactate, adenosine triphosphate, varying pH) stimulation of the muscles compared to uninjured controls. However, we found an increase in firing to heat stimuli specifically in muscle afferents during prolonged ischemia, but a distinct increase in afferent firing to non-noxious chemicals and decreased mechanical thresholds after transient ischemia. The unique changes in afferent function observed also corresponded with distinct patterns of gene expression in the dorsal root ganglia. Thus, the development of ischemic myalgia may be generated by unique afferent-based mechanisms during prolonged and transient ischemia. ⋯ This study analyzed the response properties of thinly myelinated group III and unmyelinated group IV muscle afferents during prolonged and transient ischemia in addition to pain behaviors and alterations in DRG gene expression in the mouse. Results suggest that mechanisms of pain generation during prolonged ischemia may be different from ischemia/reperfusion.
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Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. ⋯ The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world.
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Randomized Controlled Trial
Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central poststroke pain.
Central poststroke pain (CPSP) is caused by an encephalic vascular lesion of the somatosensory pathways and is commonly refractory to current pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) can change thermal pain threshold toward analgesia in healthy subjects and has analgesic effects in acute postoperative pain as well as in fibromyalgia patients. However, its effect on neuropathic pain and in CPSP, in particular, has not been assessed. The aim of this prospective, double-blind, placebo-controlled study was to evaluate the analgesic effect of PMC/DLPFC rTMS in CPSP patients. Patients were randomized into 2 groups, active (a-) rTMS and sham (s-) rTMS, and were treated with 10 daily sessions of rTMS over the left PMC/DLPFC (10 Hz, 1,250 pulses/d). Outcomes were assessed at baseline, during the stimulation phase, and at 1, 2, and 4 weeks after the last stimulation. The main outcome was pain intensity changes measured by the visual analog scale on the last stimulation day compared to baseline. Interim analysis was scheduled when the first half of the patients completed the study. The study was terminated because of a significant lack of efficacy of the active arm after 21 patients completed the whole treatment and follow-up phases. rTMS of the left PMC/DLPFC did not improve pain in CPSP. ⋯ The aim of this double-blind, placebo-controlled study was to evaluate the analgesic effects of rTMS to the PMC/DLPFC in CPSP patients. An interim analysis showed a consistent lack of analgesic effect, and the study was terminated. rTMS of the PMC/DLPFC is not effective in relieving CPSP.