Neuropathic Pain is pain caused by damage to actual nerve tissue. This can involve demyelination, transection, pressure necrosis, entrapment, neuroma formation, inflammatory nerve damage, infectious injury, infarction, autoimmune damage and sympathetic coupling. This type of pain is usually quite severe and often involves non-dermatomal patterns due to collateral nerve ectopy induction.

Physiologically, nerve stimulation occurs by two distinct processes, transduction and stimulus encoding. Transduction involves the propagation of ion flows through transmembrane channels that stimulate transmembrane electrical currents at axon end terminals. The second process is stimulus encoding, which involves a cascade of stimuli that builds up to cross a threshold, causing repetitive nerve cell firing. Stimulus encoding involves generation of extra sodium channels in the damaged end of the nerve axons.

Ectopy is an important factor in Neuropathic pain. Ectopic firing of nerve cells occurs when nerve fibers that normally do not transmit pain, A-ß touch fibers, begin to be pain responsive. This sensitization occurs when Dorsal Root Ganglion Cells become hypersensitive to nerve pain impulses. This is further complicated by wind-up in the Dorsal Horn Cell bodies through sprouting of A-ß mechanical and touch fibers into the superficial areas of the Dorsal Horn and activation of Glutamate specific postsynaptic NMDA receptors located there . Virtually all sustained neuropathic pain will cause central sensitization (central pain). If touch fibers alone are affected the patient experiences paresthesias only, but if their is recruiting of local pain transmitting nerves (C fiber and A-Delta fibers), hyperpathia and allodynia are experienced, with paroxysms of electrical or stabbing pain, quite prominent. These paroxysms may represent stimulus encoding thresholds being exceeded in bursts of activity.

Treatment for neuropathic pain can be as complex as the numerous underlying causes of this pain. If there is surgically correctable disease, the pressure on the nerve should be addressed and removed. If, on the other hand, the patient has a demyelinating illness, treatment with tricyclic analgesics may be the best place to start. In general, for non-progressive, neuropathic pain a combination of opioids at higher doses and synaptic membrane stabilization makes the most sense. Opioids need to be used at higher doses, because 65%-75% of opioid receptors are pre-synaptically located and these are damaged in damaged nerves. The remaining post-synaptic receptors need to be saturated and CNS wind-up, caused by NMDA receptor proliferation, will induce opioid tolerance. Stabilizing synaptic membranes is most often accomplished with a variety of medications, such as Lidocaine, Anti Epilepsy Drugs, Amantadine, Mexillitine, NMDA receptor blocking drugs and possibly tricyclic analgesics. If there is an inflammatory component to the neuropathic pain from irritation of the nerve and subsequent swelling of the injured nerve in a restrictive space, NSAID treatment can be helpful. Alpha 2 agonists in an intrathecal pump may be quite effective, but are not effective orally. Implantation of an intrathecal pump, after failure of oral therapy, may be very helpful due to low side effects, avoidance of first pass metabolism, and novel combinations of opioids, local anesthetics, Clonidine and/or Baclofen. Blocks with a combination of local anesthetic and steroids can provide diagnostic information and therapeutic relief.