Pain
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Accumulating evidence has demonstrated that tumor necrosis factor-alpha (TNF-alpha) plays an important role in neuropathic pain. Recently, it has been shown that Lumbar 5 ventral root transection (L5 VRT) induces persistent mechanical allodynia and thermal hyperalgesia in bilateral hind paws. In the present study, the role of TNF-alpha in the L5 VRT model was investigated. ⋯ Intraperitoneal injection of thalidomide, an inhibitor of TNF-alpha synthesis, started at 2h before surgery, blocked mechanical allodynia and thermal hyperalgesia. However, the drug failed to reverse the abnormal pain behaviors, when it was applied at day 7 after surgery. These data suggest that the upregulation of TNF-alpha and TNFR1 in DRG and spinal dorsal horn is essential for the initiation but not for maintenance of the neuropathic pain induced by L5 VRT.
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There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors. ⋯ Sham-5,7DHT and sham-saline animals showed very little response sensitivity on either hindpaw. This 5-HT-mediated difference in behaviour was independent of both the up-regulation of the NK1 receptor and spinal microglial activation produced by nerve injury. These data suggest that supraspinal serotonergic influences under these conditions are facilitatory and are implicated in the maintenance of spinal cord neuronal events leading to the behavioural hypersensitivity manifested after peripheral nerve damage.
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Systemic administration of morphine induced a hyperalgesic response in the hot plate test, at an extremely low dose (1-10 microg/kg). We have examined in vivo whether morphine, at an extremely low dose, induces acute central hypernociception following activation of the opioid receptor-mediated PLC/PKC inositol-lipid signaling pathway. The PLC inhibitor U73122 and the PKC blocker, calphostin C, dose dependently prevented the thermal hypernociception induced by morphine. ⋯ When mice were treated with a morphine analgesic dose (7 mg/kg), the downregulation of PLCbeta3 or PKCgamma at the same aODN doses used for the prevention of the hyperalgesic effect induced, respectively, a 46% and 67% potentiation in analgesic response. Experimental and clinical studies suggest that opioid may activate pronociceptive systems, leading to pain hypersensitivity and short-term tolerance, a phenomenon encountered in postoperative pain management by acute opioid administration. The clinical management of pain by morphine may be revisited in light of the identification of the signaling molecules of the hyperalgesic pathway.
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Patient adjustment to chronic pain is well known to be influenced by the spouse and his or her response to patient expressions of pain. However, these responses do not occur in a vacuum, and the aim of the present study was to investigate patient-spouse interactions in chronic pain in detail. Ninety-five patient-spouse dyads completed questionnaires relating to mood, marital satisfaction and communication, and 80 couples also took part in semi-structured interviews. ⋯ Spouse perceived frequency of pain talk was not related to spouse marital satisfaction. There were no gender differences in marital satisfaction. The results of this study challenge some of the assumptions that have been held regarding chronic pain patient-spouse interactions.