Pain
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This manuscript describes the development and initial validation of a self-report questionnaire designed to assess an individual's readiness to adopt a self-management approach to their chronic pain condition. Theory and preliminary empirical work informed the development of a pool of items that were administered to a sample of individuals reporting chronic pain. ⋯ Each of the four factors, precontemplation, contemplation, action, and maintenance, was found to be internally consistent and stable over time. There was also substantial support for each factor's discriminant and criterion-related validity.
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Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG.
Chronic loose constriction of the sciatic nerve produces mechanoallodynia and thermal hyperalgesia in rats and mice, and the behaviour develops during the time in which the nerve distal to the ligature site is undergoing Wallerian degeneration. There is a sympathetic component to the pain generated by this and other rodent models of neuropathic pain, yet the site at which this sympathetic-sensory coupling remains unknown. It has been shown that following sciatic nerve transection or spinal nerve lesion, sympathetic axons invade the dorsal root ganglion (DRG) where they sometimes form pericellular baskets around mostly large diameter DRG neurons--a possible anatomical substrate for sympathetically maintained pain (SMP). ⋯ We found that both indices of neuropathic pain were significantly attenuated in Wld mice compared to wild-type mice, with the wild-type mice increasing in sensitivity to both thermal and mechanical stimulation in the first week post-operative (PO), while Wld mice showed marked hypoalgesia following CCI. Histological examination of the DRG showed that sympathetic sprouting into the DRG was also markedly delayed in Wld mice compared to wild-type mice: 1 week following injury, sympathetic fibres had invaded the ipsilateral DRG of wild-type mice, while sprouting in ipsilateral DRG of Wld mice was only slightly increased at 3 weeks PO. These results show that Wallerian degeneration is tightly linked to the development of both pain and sympathetic sprouting following CCI, and we speculate on the possible role of NGF as a mediator of both phenomena.
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Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid rotation is often necessary in the event of toxicity and/or inadequate analgesia. Equianalgesic reference tables based on single dose comparisons are possibly inadequate for patients on chronic treatment and developing tolerance. ⋯ Our data suggests that HM is 5 times more potent than M when given second (M-HM), but is only 3.7 times more potent when given first (HM-M). We therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of 3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids. There was no correlation observed between M-HM and HM-M dose ratios and the level of previous opioid dose, in contrast to HM to methadone rotation where the dose ratio was higher in patients receiving higher doses of HM.
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Neuropathic pain or persistent dysesthesias may be initiated by mechanical, chemical, or ischemic damage to peripheral sensory nerves. In animal models of neuropathic pain, transection or constrictive injury to peripheral nerves produces ectopic discharges originating at both injury sites and related dorsal root ganglia (DRG), and, consequently, hyperexcitability in associated dorsal horn (DH) neurons of the spinal cord. Since ectopic discharges are inhibited by agents that block voltage-sensitive Na+ channels, it has been postulated that accumulation of Na+ channels in the membrane at nerve injury sites may contribute to, or be responsible for, the development of ectopic neuronal activity (ENA). ⋯ Inhibition of ENA in neuromas and DRG did not recover within 10 min after 100 or 300 microg/kg TTX. By comparison, the ED50 value for the initial decrease of HR was 17.9 (15.0-21.5) microg/kg, and partial recovery occurred within approximately 3 min. These data support the hypothesis that Na+ channel accumulation contributes to the generation of ectopic discharges in neuromas and DRG, and suggest that TTX-sensitive Na+ channels located at the nerve injury site and DRG play an important role in the genesis of neuropathic pain.
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Subcutaneous (s.c.) injection of formalin induces a rapid and prolonged hyperalgesia across widespread areas of the body. This hyperalgesic state involves a brain-to-spinal cord pathway, likely arising from the nucleus raphe magnus. The present study examined whether subsequent activation of spinal cord glia may be critical for the hyperalgesic state to be observed in rats. ⋯ Disruption appeared to be selective, as blockade of only select glial products was effective. That is, up to 120 microg of a functional antagonist of tumor necrosis factor-alpha (TNF binding protein) and 5 microl of an antibody against complement-3 produced no statistically reliable reduction in formalin-induced hyperalgesia. Taken together, the present series of experiments suggest an important role for spinal glial cells in the cascade of events that are initiated by descending signals following s.c. administration of formalin.