Pain
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Comparative Study
Use of a novel thermal operant behavioral assay for characterization of orofacial pain sensitivity.
Orofacial pain has been well-characterized clinically, but evaluation of orofacial pain in animals has not kept pace. The objective of this study was to describe behavioral responses to facial thermal stimulation and inflammation with/without an analgesic using a novel operant paradigm. Animals were trained to voluntarily place their face against a stimulus thermode (37.7-57.2 degrees C) providing access to positive reinforcement. ⋯ These outcomes were significantly affected in the direction of increased nociception following inflammation, and these indices of hyperalgesia were reversed with morphine administration. These data reflect an orofacial pain behavior profile that was based on an animal's responses in an operant escape paradigm. This technique allows evaluation of nociceptive processing and modulation throughout the neuraxis.
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Comparative Study
Comparative actions of the opioid analgesics morphine, methadone and codeine in rat models of peripheral and central neuropathic pain.
Controversy persists in relation to the analgesic efficacy of opioids in neuropathic pain. In the present study the effects of acute, subcutaneous administration of the mu-opioid receptor agonists morphine, methadone and codeine were examined in rat models of peripheral and central neuropathic pain. In the spared nerve injury (SNI) and chronic constriction injury (CCI) models of peripheral neuropathic pain, both morphine (6mg/kg) and methadone (3mg/kg) attenuated mechanical allodynia, mechanical hyperalgesia and cold allodynia for up to 1.5h post-injection (P<0.05); codeine (30mg/kg) minimally alleviated mechanical hypersensitivity in SNI, but not CCI rats. ⋯ The therapeutic window (based on antiallodynia versus ataxia) obtained for codeine, was vastly superior to that obtained with morphine or methadone in SNI and SCI rats. Furthermore, the therapeutic window for codeine in SCI rats was 4-fold greater than in SNI rats. Our results further support the efficacy of mu-opioid receptor agonists in alleviating signs of neuropathic pain in animal models of peripheral and especially central nerve injury.
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Identifying individual differences in pain is an important topic; however, little is known regarding patterns of responses across various experimental pain modalities. This study evaluated subgroups emerging from multiple experimental pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal pain assessments. ⋯ Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different pain modalities in order to more accurately characterize individual differences in responses to experimental pain.
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Comparative Study
Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain.
Proinflammatory cytokines are mediators of inflammatory and neuropathic pain. Here, we investigated pain-related behavior in rats after intraneural injection of different doses of rat recombinant interleukin-1beta (rrIL-1beta) and tumor necrosis factor-alpha (rrTNF) into the sciatic nerve. Doses ranged between 0.25 and 2500pg/ml for rrIL-1beta and 0.25-250pg/ml for rrTNF. ⋯ However, this did not reflect the extent of behavioral changes. In summary, we found a bell-shaped dose-response curve for the algesic effects of rrIL-1beta and rrTNF, peaking at doses equivalent to those of endogenous cytokines released locally after nerve injury. The absence of corresponding morphological changes in nerves supports the concept of a functional effect of the cytokines at these doses.
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Comparative Study
Effects of gabapentin on spontaneous discharges and subthreshold membrane potential oscillation of type A neurons in injured DRG.
Ectopic spontaneous discharges play a critical role for both initiation and maintenance of the neuropathic pain state. Gabapentin (GBP) has been shown to be effective in animal models of neuropathic pain as well as in chronic pain patients. To investigate the peripheral mechanisms of GBP, the effects of GBP on spontaneous discharges and subthreshold membrane potential oscillation (SMPO) of chronically compressed dorsal root ganglion (DRG) were examined electrophysiolocally in vitro. ⋯ Furthermore, we found that the SMPO of injured DRG cells can be selectively abolished by GBP without interrupting spike propagation. The results suggest that the inhibitory effect of GBP on SMPO might be one of the membrane mechanisms of action of GBP. This may partially explain the antinociceptive action of GBP by directly suppression nociceptive afferent input to the spinal cord.