Pain
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Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally. It is currently under clinical investigation for the treatment of malignant and non-malignant pain syndromes. The present study was undertaken to compare and contrast antinociceptive properties of ziconotide, morphine and clonidine in a rat model of post-operative pain. ⋯ Intravenous bolus injection of 3 mg/kg (1.1 micromol/kg) ziconotide, administered either before or after incisional surgery, had no effect on thermal pain thresholds measured in either the injured or normal hindpaw. In contrast, intraperitoneal injections of 2 mg/kg (2.6 micromol/kg) morphine and 2.5 mg/kg (9.4 micromol/kg) clonidine blocked heat hyperalgesia in the injured hindpaw; morphine, but not clonidine, also elevated thermal (heat) nociceptive response thresholds in the normal hindpaw. The results of this study show that intrathecal ziconotide is antinociceptive in a rat incisional model of post-operative pain and is more potent, longer acting, and more specific in its actions than intrathecal morphine.
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Randomized Controlled Trial Clinical Trial
Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia.
Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain. The purpose of the current study was to estimate the relative potency of clonidine by epidural and intrathecal routes in the treatment of capsaicin-induced hyperalgesia and allodynia as a model of central hypersensitivity and of noxious heat as a model of acute pain. Twenty-four healthy volunteers were randomized to receive either intrathecal clonidine (75, 150, or 300 micrograms) or epidural clonidine (150, 300, or 600 micrograms) and rated pain from a Peltier-controlled thermode at a lumbar, thoracic, and cervical dermatomal site before and after drug administration. ⋯ For acute thermal pain, intrathecal clonidine produced a dose-dependent analgesia with a lumbar>thoracic>cervical gradient, whereas only one dose of epidural clonidine reduced thermal pain and this was at the thoracic testing site. In contrast, the potency of clonidine to reduce capsaicin-induced allodynia was similar between the two routes of injection, and for hyperalgesia, clonidine was only slightly more potent after intrathecal than epidural injection. These data support clinical studies from non-comparative trials and suggest there is a >6-fold potency ratio of intrathecal:epidural administration of clonidine for acute pain, but a <2-fold potency ratio for these routes for mechanical hypersensitivity.
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Clinical Trial
Predicting responses to self-management treatments for chronic pain: application of the pain stages of change model.
Psychological treatments emphasizing a self-management approach have become commonly accepted alternatives to medical interventions for chronic pain. Unfortunately, these approaches often fail to engage a significant portion of targeted individuals and are associated with high drop-out and relapse rates. Informed by the transtheoretical model of behavior change and the cognitive behavioral perspective on chronic pain, the Pain Stages of Change Questionnaire (PSOCQ) was developed to assess readiness to adopt a self-management approach to chronic pain. ⋯ Separate analyses revealed that Action and Maintenance scores increased over the course of treatment, and that changes in the PSOCQ scales were associated with improved outcomes. These findings suggest that increased commitment to a self-management approach to chronic pain may serve as a mediator or moderator of successful treatment. This study supports the predictive validity and utility of the PSOCQ, as well as the relevance of the stages of change model to self-management of chronic pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Fear and anxiety: divergent effects on human pain thresholds.
Animal studies suggest that fear inhibits pain whereas anxiety enhances it; however it is unclear whether these effects generalize to humans. The present study examined the effects of experimentally induced fear and anxiety on radiant heat pain thresholds. Sixty male and female human subjects were randomly assigned to 1 of 3 emotion induction conditions: (1) fear, induced by exposure to three brief shocks; (2) anxiety, elicited by the threat of shock; (3) neutral, with no intervention. ⋯ Pain rating data indicated that participants used consistent subjective criteria to indicate pain thresholds. Both subjective and physiological indicators (skin conductance level, heart rate) confirmed that the treatment conditions produced the targeted emotional states. These results support the view that emotional states modulate human pain reactivity.