- The Foundation For Peripheral Neuropathy - https://www.foundationforpn.org -

Etiology and Pharmacology of Neuropathic Pain

Treatment Options for Neuropathic Pain

Pain is a common reason for people to seek medical attention. Pain is vital – it is a survival mechanism that protects us from injury. Injury to nerve tissue will cause nerve pain (or neuropathic pain) that can last for months or years after the initial injury has healed.

Many patients with peripheral neuropathy [1] experience neuropathic pain. Its true prevalence is unknown, but it is estimated that about 100-500 million patients are living with neuropathic pain worldwide. Treatment of neuropathic pain is also challenging and available medications are not very effective.

Pharmacological Review

In a recent medical review article entitled, Etiology and Pharmacology of Neuropathic Pain [2], Sascha R. A. Alles and Peter A. Smith from the University of British Columbia and the University of Alberta tried to explain the medical evidence behind the generation and the maintenance of neuropathic pain and how this can help identify new treatments for neuropathic pain.

They started by taking us through the anatomical pathways of neuropathic pain, and how its generation in the periphery alters normal pain transmission circuitry within the brain and throughout the spinal cord, creating central sensitization or a persistent abnormal memory of pain.  This altered pain and sensory perception is mediated by increased firing of certain sensory neurons, an abnormal neurotransmitter response, as well as an abnormal gating of certain channels like calcium and sodium channels.

In this review, Alles and Smith explain how small molecule manipulation of the channels that serve as sensory receptors, such as certain calcium, sodium and potassium channels, the activated cyclic nucleotide gated channels, the transient receptor potential type V1 channel, and/or the Adenosine A3 Receptor – all which could be new therapeutic targets. By manipulating these channels, the perception of pain could be modified.

Prescribing Gabapentinoids

Despite all this progress in our understanding of neuropathic pain, gabapentinoids (Gabapentin and Pregabalin) remain our go-to treatment [3] even though their exact mechanism of action is poorly understood.

Understanding the molecular mechanisms of neuropathic pain also helped shed some light on the mechanisms of action of Gabapentin.  Gabapentin binds to a special sub-unit of the calcium channel, producing specific and nonspecific effects in the spinal cord and the brain. This impacts the perception of pain and could be further enhanced by future therapeutics. New therapies that can affect multiple targets simultaneously like Gabapentin seem to have the highest promise.