Pharmacological Approach to the Treatment of Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is neuropathic pain syndrome. PHN occurred after herpes zoster which causes the peripheral nerve inflammation. PHN has been known to be relatively refractory to the standard analgesic agents, such as non-steroidal anti-inflammatory drugs and opioids. Anti-depressant drugs, anti-arrhythmic drugs and anti-convulsants are usually used for the treatment of PHN, but the results of this treatment are not always satisfactory.<br>N-methyl-D-aspartate (NMDA) receptor dependent spinal sensitization has been shown to play an important role in the maintenance of neuropathic pain and NMDA receptor antagonists have been reported to alleviate the level of neuropathic pain in the animal model. Ketamine and dextromethorphan are the clinically available NMDA receptor antagonists and I tried to treat PHN with epidural ketamine and oral dextromethorphan. Both epidural ketamine and oral dextromethorphan successfully treated PHN. This suggested that PHN is maintained by the NMDA receptor dependent spinal sensitization.<br>Recently, three new pharmacological approaches, such as systemic gabapentin administration, intrathecal admnistration of N-type voltage dependent Ca²⁺channel (VDCC) blocker and intrathecal nociceptin injection, have been tested for the treatment of neuropathic pain in the animal models. Gabapentin is a newly developed anti-convulsant drug. Oral gabapentin has already reported to treat PHN in the clinical situation. Release of neurotransmitter is regulated by the influx of Ca²⁺ into the nerve terminals through VDCCs, such as N-type VDCC. N-type VDCC blockers inhibit the substance P and glutamate release and intrathecal injection of N-type VDCC attenuates the level of neuropathic pain in the animal model. Nociceptin is an endogenous agonist for the opioid receptor likel receptor. Nociceptin has been reported to depress the spinal sensitization and to alleviate the level of neuropathic pain in the animal model. I believe that these three drugs will be the major approach to the treatment of PHN in near future.