By Steven B. Graff-Radford, DDS
The trigeminal nervous system is primarily a sensory system supplying the face and oral structures. There are four peripheral mechanisms that may be involved in chronic trigeminal neuropathic pain development: nerve compression, nerve regeneration, sympathetically maintained pain and immune mediated pain.
Nerve compression: When a peripheral nerve is compressed or injured, there is a sustained firing that may be persistent. The closer the damage is to the central nervous system, the longer is the spontaneous neural discharge. This may be demonstrated with recordings in the trigeminal nucleus in animals that have received a compressive injury (e.g., tooth pulp removal or ligatures tied around the nerve). Clinically this may develop after a perfect endodontic treatment, a wisdom tooth extraction or other well-executed surgery. The pain following nerve compression is a constant burning, aching pain, which can be temporarily relieved with local anesthetic blockade. This neural trauma may also result in receptor sprouting on the nociceptor, dorsal horn cells and peripheral blood vessels. These may include alpha-receptors, NPY receptors and possibly others. There is also an increase in trigeminal nucleus substance P, CGRP and other neurotransmitter release, resulting in further neurogenic inflammation and chronic pain.
Nerve regeneration: Neuroma formation is essentially created by nerve regeneration where the path for regrowth is obstructed. The nerve resprouting and the continuous nerve irritation may result in pain. As in nerve compression, receptor sprouting and neurotransmitter presence will increase the pain. Injecting the neuroma with local anesthetic will temporarily block the pain. The sprouting axons acquire abnormal properties. They fire spontaneously and develop abnormal sensitization to norepinepherine, cold and mechanical stimulation. This occurs in dorsal root ganglion cells, as well as peripheral terminals. Clinically the neuroma may only produce pain following mechanical stimulation.
Sympathetically maintained pain: Campbell best summarizes this phenomenon. He has reported that the initial trauma to the peripheral nervous system activates nociceptors and produces a sprouting of alpha-adrenergic receptors on the nociceptors. Additionally, the initial sensory barrage sensitizes the CNS, causing sympathetic afferent activation. This causes peripheral norepinepherine release, which further activates the peripheral nociceptors and keeps the cycle active. There is evidence that following neural injury the sympathetic innervation in the dorsal root ganglia increases with age. It is not surprising that there is a higher incidence of neuropathic pain as we age. The CNS sensitization allows for non-noxious stimuli to activate the CNS. Hence, touch is perceived as painful. The clinical picture includes persistent pain in the presence of allodynia that can be aggravated by non-noxious stimuli and interrupted temporarily by sympathetic block or alpha-adrenergic block with phentolamine.
Immune mediated pain requires the presence of tissue injury by a viral or bacterial infection to trigger macrophage activity and the release of interleukin 1, 6 and tissue necrosis factor. This in turn activates the nucleus tractus solitarius via the vagus nerve. The glial cells in the spinal cord are also capable of turning on this pain response. The pain can be inhibited by interleukin 10. When this system malfunctions, chronic pain may ensue. It is also possible to create a mirror image of the pain if the activation peripherally is significant enough to create an endoneurial inflammation.
