Physiological rationale for the treatment of neuropathic pain

Abstract

Neuropathic pain occurs when irritation or injury of peripheral nerves causes the development of ectopic neural pacemaker sites and the degeneration of inhibitory interneurons. The type of neuropathic pain depends on the degree of nerve injury. Trigeminal nerve irritation only causes degeneration of some inhibitory interneurons leading to an excessive response of low-threshold mechanoceptive neurons to tactile stimulation and episodic, allodynic pain when the paroxysmal firing spreads to wide dynamic range neurons. Injury to the trigeminal nerve causes destruction of low-threshold mechanoceptive neurons and more extensive loss of inhibitory interneurons, leading to continuous overreaction of wide dynamic range neurons perceived as ongoing pain. Drugs that are GABA-B agonists and kainic acid antagonists should be effective in the treatment of episodic and allodynic pain, and drugs that are GABA-A agonists and NMDA antagonists should be useful in the treatment of ongoing neuropathic pain.