Pain
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The analgesic effect of intrathecal injection of epibatidine, clonidine and neostigmine, compounds that elevate ACh, was examined in the formalin test, a model of post-injury central sensitization in the rat. The compounds were injected alone and in combination. Intrathecal injection of epibatidine alone did not alter pain behaviors, compared to vehicle-treated rats. ⋯ The combination of neostigmine and epibatidine, in a ratio of 8:1, significantly shifted the dose response curve 4-fold to the left (ED(50)=0.4+/-0.3 microg). The effect is mediated in part by the activation of the nAChR and possibly by the enhanced release of ACh. These data demonstrate significant enhancement of the antinociceptive effects of spinally delivered analgesics by a nAChR agonist, suggesting that this class of compounds may have utility as adjuvants when combined with conventional therapeutics.
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Randomized Controlled Trial Clinical Trial
Habituation of the early pain-specific respiratory response in sustained pain.
Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm when injected directly into the preBötzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such considered independent of the activation of the mu-opioid system. Prolonged application of electrical shocks, however, produces analgesia that is mediated by the mu-opioid system (Science 208 (1980) 623). ⋯ In the early stage of pain, all monitored variables (respiration rate, minute ventilation volume, and inspiratory and expiratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Only respiration rate continued to be significantly elevated in sustained pain. We concluded that rhythmogenic neurons in the preBötzinger brainstem complex appear as the likely target for pro-nociceptive and anti-nociceptive input, explaining both the observed initial facilitation and subsequent habituation of respiration in early and sustained pain.
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Randomized Controlled Trial Clinical Trial
A cognitive-behavioral return-to-work program: effects on pain patients with a history of long-term versus short-term sick leave.
A cognitive-behavioral return-to-work focused program was evaluated in a randomized controlled design, and the effects were compared between two groups of women with musculoskeletal pain. One group of patients (n=36) had a history of long-term sick leave (>12 months) at the start of the program and the other (n=36) had a history of short-term sick leave (2-6 months). The outpatient treatment program, conducted by a psychologist, included 12 sessions with the primary aim to help the patients return-to-work. ⋯ The results showed that the cognitive-behavioral return-to-work program was more effective than the treatment-as-usual control condition in reducing the number of days on sick leave for patients on short-term sick leave, but not for patients on long-term sick leave. The treatment program also helped the patients on short-term sick leave to increase their ability to control and decrease pain and to increase their general activity level compared to the control condition. These results underscore the need for an early return-to-work focused rehabilitation to prevent long-term sick leave and disability.
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Although individuals with fibromyalgia syndrome (FMS) consistently report wide-spread pain, clear evidence of structural abnormalities or other sources of chronic stimulation of pain afferents in the involved body areas is lacking. Without convincing evidence for peripheral tissue abnormalities in FMS patients, it seems likely that a central pathophysiological process is at least partly responsible for FMS, as is the case for many chronic pain conditions. Therefore, the present study sought to obtain psychophysical evidence for the possibility that input to central nociceptive pathways is abnormally processed in individuals with long standing FMS. ⋯ Within series of stimuli, FMS subjects reported increases in sensory magnitude to painful levels for interstimulus intervals of 2-5 s, but pain was evoked infrequently at intervals greater than 2 s for control subjects. Following the last stimulus in a series, after-sensations were greater in magnitude, lasted longer and were more frequently painful in FMS subjects. These results have multiple implications for the general characterization of pain in FMS and for an understanding of the underlying pathophysiological basis.
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Comparative Study
Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy.
Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. ⋯ The effects of MK-801 were comparable between SNL and sham operated rats for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical evoked responses). The differential blocking abilities of these antagonists on the various neuronal responses may relate to the characteristics of their voltage-dependent blockage of the channel associated with the receptor. The favourable side effect profile of memantine supports its potential use for the treatment of neuropathic pain.