The journal of pain : official journal of the American Pain Society
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Previous studies in our laboratory have shown that long-term (a period of weeks) increases in pain-related behavior were correlated with the activation of spinal microglia after subcutaneous injection of formalin into the dorsal surface of 1 hind paw. The present study examined whether intrathecal delivery of suramin (a P2 receptor antagonist) blocks microglia activation and long-term hyperalgesia induced by formalin injection. Suramin was administered by using an osmotic pump attached to an intrathecal catheter. Suramin delivery (1.25 microg/kg/h) began 1 day before the formalin injection and lasted for 4 days. Rats were observed by using a modified hot plate test before and at different times after formalin injection. The spinal cord was surveyed for changes in microglia labeling as shown by OX-42 staining at different times after formalin injection. Suramin decreased both the hyperalgesic sensitivity to the thermal stimuli and microglial activation induced by formalin injection as compared to the saline-treated group. This suggests that adenosine triphosphate is one potential mediator that activates spinal cord microglia and enhances pain-related behavior in the formalin model. ⋯ This report suggests that blocking specific spinal P2 receptors might decrease the central enhancement of pain caused by peripheral injury and inflammation. One mechanism might be by blocking the activation of spinal microglia. Thus, P2 antagonists might have therapeutic usefulness in certain pain conditions.
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This article reports the development of a new hind limb pain model in which an incisional stab wound is placed on the front and back of the calf, causing both superficial and deep tissue injury. The injury causes primary mechanical hyperalgesia on the calf and secondary hind paw hyperalgesia, which served as the focus of the present study. Animals with unilateral stab wounds showed a significant increase in percent paw withdrawal (secondary mechanical hyperalgesia, reversed by morphine administration) from 2 to 48 hours after surgery, but no evidence of thermal hyperalgesia. In contrast, animals with bilateral leg injuries showed bilateral secondary mechanical and thermal hyperalgesia. Rats with unilateral leg incisional stab wounds showed a significant decrease in cage activity in both the horizontal and vertical directions, monitored by using a novel activity box approach, as compared to their 24-hour baseline levels or to the activity of naïve animals. Analysis of spinal cord Fos labeling demonstrated that calf injury significantly increased Fos expression in laminae I to VI of the L3-L5 cord segments. The data indicate that this model might be useful for evaluation of the mechanisms underlying penetrating injury-induced primary and secondary hyperalgesia or for testing the effect of analgesics on hyperalgesia induced by such injury. ⋯ Stab wounds and other types of penetrating wounds routinely encountered in emergency rooms and clinics are accompanied by pain associated with superficial and deep tissue injury. Here we present a rodent stab wound model that affords an opportunity to study the mechanisms of pain associated with traumatic injury.
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Randomized Controlled Trial Clinical Trial
Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study.
Hyperalgesia has been demonstrated to be a cardinal sign of physical withdrawal from opioids in preclinical models for more than 30 years, although few empirical data exist to support its occurrence in humans. In this preliminary study we used the acute opioid physical dependence (APD) model to test for the presence of hyperalgesia to experimental cold-pressor pain in 4 healthy non-opioid-dependent men via 3 different pretreatment opioid administration protocols previously demonstrated to induce APD (morphine 18 mg/70 kg intramuscular, morphine 10 mg/70 kg intravenous, hydromorphone 2 mg/70 kg intravenous), repeated on 2 separate occasions, and placebo. ⋯ Paired t tests comparing change scores between the opioid pretreatments and placebo showed that pain threshold and tolerance to the cold-pressor uniformly decreased across all APD induction methods, and the effect size was large (approximately 70% of baseline) and reproducible. These findings provide initial support for the existence of opioid-induced hyperalgesia, which has been conceptualized as a coexisting opponent process to opioid-induced analgesia and proposed to be an alternative explanation for the development of analgesic tolerance to opioids.
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This study set out to examine whether gender or race influences physicians' pain management decisions in a national sample of 712 (414 men, 272 women) practicing physicians. Medical vignettes were used to vary patient gender and race experimentally while holding symptom presentation constant. Treatment decisions were assessed by calculating maximum permitted doses of narcotic analgesic (hydrocodone) prescribed for initial pain treatment and for follow-up care. ⋯ However, for persistent back pain, female physicians prescribed lower doses of hydrocodone, especially to male patients. For renal colic, lower doses were prescribed to black versus white patients when the patient was female, whereas the reverse was true when patients were male. These findings challenge a fairly extensive literature suggesting that physicians treat women and minorities less aggressively for their pain, and results offer further evidence that pain treatment decisions are influenced physician gender.
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Clinical Trial
Stress influences the level of negative affectivity after forehead cold pressor pain.
The purpose of this study was to investigate simultaneously a stress manipulation and an experimental pain manipulation to determine how stress and pain interact to influence negative affectivity. One hundred healthy subjects completed a counterbalanced repeated measure crossover design in which stress (speech task) versus a nonstress control condition (magazine reading) was manipulated. Each session was immediately followed by a 2-minute forehead cold pressor task. ⋯ Regression analysis showed that the stress manipulation influenced the level of anger and that change in anger predicted post-pain negative affectivity independently of the contribution of maximum pain (model R(2) =.31), with 45% of the total model variance accounted for by change in anger and 17% of the total model variance accounted for by maximum pain intensity. In the nonstress condition only level of pain intensity was an independent predictor of negative affectivity (model R(2) =.16), with 69% of the total model variance accounted for by maximum pain intensity. These results show that stress significantly amplifies post-pain negative mood beyond that accounted for by the level of pain intensity alone.