There is still a need for a new analgesic devoid of the side effects presented by opioids or non-steroidal anti-inflammatory drugs, for the treatment of some acute and chronic pain conditions. Lamotrigine (Lamictal1, 10-100 mg/kg), a new anticonvulsant, showed analgesic effects in the acute model of prostaglandin E2 (PGE2)-induced hyperalgesia when given orally before or after the subplantar injection of PGE2 in the rat. It also inhibited the development of sustained hyperalgesia induced by multiple subplantar injections of PGE2 when administered orally prior to the PGE2 injections. Furthermore, lamotrigine induced analgesia in the model of chronic hyperalgesia in streptozotocin-induced diabetic rats. The effects of carbamazepine and phenytoin are compared to the effects of lamotrigine in this model. The results suggest that lamotrigine could be used in pain conditions where neuronal sensitization may be present and possibly also where it could inhibit the development of this sensitization.
The hyperalgesic effect of substance P (SP) is usually described as presenting short latency. We now report that multiple injections of sub-threshold doses of SP into the foot pad of a hind paw of rats pre-treated with indomethacin induced a long-lasting hyperalgesia, sensitizing the paw to further challenges with small doses of SP, dopamine or prostacyclin. The sensitizing process also occurred after multiple injections of prostacyclin or prostaglandin E2. The sensitizing effect induced by SP, prostaglandin E2 or prostacyclin is inhibited by pre-treatment with the SP antagonist (D-Arg, D-Pro, D-Trp, Leu)-SP. We suggest that SP has an important role as a modulator in peripheral inflammatory pain by sensitizing nociceptors to its own action and to the action of different mediators. This sensitizing process could also be associated with chronic inflammatory pain.
The cytokine interleukin-lf (IL-I0) is a potent hyperalgesic agent in the rat whereas IL-la is relatively inactive (Ferreira et al., 1988). IL-1fi induced a dose-dependent increase in the sensitivity of rat paws to mechanical stimulation following intra-plantar injection but this effect was not reduced by indomethacin (1.Omgkg-1, p.o.), at a dose known to inhibit completely prostaglandin synthesis in the rat (Salmon et al., 1983). Prostaglandin (PG)E2 enhanced sensitivity to both mechanical pressure and increased temperature but IL-If enhanced only sensitivity to pressure. These observations indicate that IL-I# sensitized pressuresensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism.Hyperalgesia induced by IL-1f but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (aMSH) and its analogue [Nle',
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