What Is The Physiological & Pharmacological Basis For Anti-depressants & Anti-convulsants In The Management Of Neuropathic Pain?

Introduction

It’s been newly proposed to define neuropathic pain as: “Pain arising as a direct consequence of a lesion or a disease affecting the somatosensory nervous system”(1)

The sites of the disorders giving rise to neuropathic pain are likewise multiple and dispersed, extending from the terminal nerve fibres to the highest centres in the cerebral cortex. (2)

It’s been recently suggested that neuropathic pain may affect as much as 3% of the population.(3) Those affected have described their pain with words such as “punishing-cruel”, “tiring-exhausting”. Evidence shows that neuropathic pain impairs patients’ mood, their relationships, health-related quality of life, activities of daily living and performance at work, thus experiencing low utilities, which will not only impact their life but also the life of their families. (3,4,5,6,7)

Pathophysiological mechanisms include sodium and calcium-channel upregulation, spinal hyperexcitability, descending facilitation and aberrant sympathetic-somatic nervous system interactions. (3)

An evidence-based review for the pharmacologic management of neuropathic pain recommends as first-line treatment: Tricyclic antidepressants (TCAs) and selective serotonin and norepinephrine reuptake inhibitors (SSNRIs); Calcium channel α2-δ ligands and topical lidocaine. (8)

The pharmacological approach of affective disorders has its origin in the 50’s decade, same decade where the first antipsychotic and anxiolytic agents were developed, with the introduction of the tricyclic’s Imipramine and Iproniazid. Since then, several compounds have been synthesized with different mechanisms of action. (9)

Antidepressants mainly act by inhibiting the reuptake of serotonin (5-HT) and norepinephrine (NE), thus extending the exposure of the neurons to these neurotransmitters. (10)

On the other hand, anticonvulsants where designed to modify the neuronal excitability responsible for the convulsions, acting over ionized channels with the aim of favouring the inhibition over the excitation thus avoiding or preventing an epileptic crisis. (11)

The aim of this essay is to explore the different mechanisms of action, from a physiological and pharmacological point of view for two different tricyclic antidepressants (amitriptyline and nortriptyline) and two different anticonvulsants calcium channel α2-δ ligands (gabapentin and pregabalin) in neuropathic pain. Also, to compare the variability in their effects within the general population, being able to determine which administration routes, drug amounts, etc. are optimal after looking at this drugs pharmacokinetics.

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