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New Analgesics for Neuropathic Pain

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Glutamate is a neurotransmitter, which plays a role in central sensitization. Lamotrigine blocks both neuronal sodium channels as well as inhibits excessive release of glutamate. Studies have shown that lamotrigine could inhibit hyperalgesia and allodynia (Nakamura-Craig & Follenfant, 1992). In another placebo-controlled study, lamotrigine, when used along with moderate doses of carbamazepine could control the pain in refractory trigeminal neuralgia (Zakrewska et al. ,1997). In addition to neuropathic pain, there is evidence that lamotrigine is effective in reducing central pain, which is otherwise difficult to reduce, although this is possible only at high doses of 600 mg/day (Canavera & Bonicalzi, 1996).

Common adverse effects include skin complications, which could be severe; other adverse effects are similar to that of other anticonvulsants. A low initial dose of 25 to 50 mg/day with a gradual increase of the dose, reduces the risk of side effects (Nurmikko, 1998). Recently, the role and function of the KCNQ K+ family of channels (Kv7) in the regulation of neuronal excitability and nociception have been discussed. Since they are located in the spinal cord, dorsal root ganglion, and CNS, they are an ideal target in the treatment of neuropathic pain.

All KCNQ channels have the ability to couple to muscarinic receptors and form M-currents, which are inhibited by acetylcholine. The prototypical Kv7 channel opener is retigabine, which is basically an anticonvulsant. In rodent models, retigabine and its analogs have been found to attenuate neuropathic and nociceptive pain behaviors, and are able to hyperpolarize neuronal cells (Butera, 2007.) Tramadol is a weak opiate, which acts centrally. It modulates central serotoninergic and noradrenergic inhibition of pain. The risk of addiction is low.

Some of the adverse effects include dizziness, sedation, and nausea (Nurmikko, 1998). Meloxicam has a selective inhibitory action on the enzyme cyclooxygenase 2 (less on cyclooxygenase 1).

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