Pain
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Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. ⋯ AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors.
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We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA-related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single-injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients). ⋯ There was also evidence of a decrease in the risk of shivering (risk ratio [RR]: 0.26; 95% confidence interval [CI]: 0.12-0.56), nausea (RR: 0.45; 95% CI: 0.31-0.66), and arterial hypotension (RR: 0.52; 95% CI: 0.35-0.78). The risk of pruritus was increased (RR: 11.7; 95% CI: 6.2-21.9). Adding an opioid to a reduced dose of an intrathecal LA can decrease LA-related adverse effects and improve recovery from the spinal block without compromising intraoperative anesthesia or duration of postoperative analgesia.
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The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions, including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to interindividual variability in pain phenotypes such as sensitivity to noxious stimuli, severity of clinical pain, and response to pain treatment. In this study, we found that the effects of Comt functional variation in mice are modality specific. ⋯ The ancestral Comt variant, without a B2 SINE insertion, was more strongly associated with sensitivity to capsaicin in female vs male mice. In humans, the haplotype coding for low COMT activity increased capsaicin-induced pain perception in women, but not men. These findings reemphasize the fundamental contribution of COMT to pain processes, and provide a fine-grained resolution of this contribution at the genetic level that can be used to guide future studies in the area of pain genetics.
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Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. ⋯ Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P=.035 and P=.019), and significantly increased after rTMS (P=.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP.