Drug Targets of Migraine and Neuropathy: Treatment of Hyperexcitability

Abstract

Migraine and neuropathic pain are common causes of chronic pain. The exact pathomechanism has not been fully clarified for either disorder, but their pathophysiological backgrounds involve several similar mechanisms. Peripheral sensitization occurs in the neuronal elements of the dorsal root ganglion or the trigeminal ganglion, while central sensitization appears in the second-order neurons in the dorsal horn of the spinal cord or the trigeminal nucleus caudalis. Central neuronal hyperexcitability has been implicated in both disorders, and the emerging evidence suggests alterations in the glutamatergic neurotransmission and N-methyl-D-aspartate-receptor activation. Migraine and neuropathic pain additionally share certain clinical features, such as enhanced sensitivity to sensory stimuli and cutaneous allodynia. The pharmacotherapy of both diseases is often challenging, but several antiepileptic drugs that target hyperexcitability are beneficial for both migraine and neuropathic pain. Kynurenine pathway metabolites are capable of influencing the glutamate receptors, and might therefore be novel candidates for future drug development.

Research : Use of Dry Electroencephalogram and Support Vector for Objective Pain Assessment

“…21,22 It was noted that majority of these studies also found that θ and α band changes were in highest correlation with pain, and it was suggested by Pinheiro et al that increases in θ band power could serve as a biomarker in severe neuropathic pain. 23,20 We saw similar changes in all frequency bands. Yet, due to our sample size, it will take conducting a larger study perhaps with more than one pain modality to make any valid conclusion.…”

Interactions between the Kynurenine and the Endocannabinoid System with Special Emphasis on Migraine

“…Human and animal data show that migraine is presumably hyperexcitability disorder, which means that the glutamatergic system is overactive [ 7 ]. In addition, an increasing amount of evidence suggests that migraine could alsobe linked to the kynurenine pathway (KP) itself [ 8 ].…”

Alleviation of pain in painful diabetic neuropathy

“…Neuropathic sensory symptoms characterized by spontaneous or evoked pain is described as electric shock-like or burning, and other sensory disturbances such as paraesthesia, dysaesthesia, allodynia, hyperpathia or hyperalgesia. The symptoms of painful diabetic neuropathy (PDN) occur symmetrically in the distal parts of the extremities in an ascending manner [4,5] . The aetiology of NP involves a wide range of peripheral or central nervous system (CNS) disorders, including diabetic and other metabolic neuropathies, dysimmune neuropathies, postherpetic neuralgia, trigeminal neuralgia, human immundeficiency virus (HIV)-associated neuropathy or pain after spinal cord injury, poststroke pain, multiple sclerosis-associated pain or cancer-related pain [5] .…”

“…The symptoms of painful diabetic neuropathy (PDN) occur symmetrically in the distal parts of the extremities in an ascending manner [4,5] . The aetiology of NP involves a wide range of peripheral or central nervous system (CNS) disorders, including diabetic and other metabolic neuropathies, dysimmune neuropathies, postherpetic neuralgia, trigeminal neuralgia, human immundeficiency virus (HIV)-associated neuropathy or pain after spinal cord injury, poststroke pain, multiple sclerosis-associated pain or cancer-related pain [5] . Diabetes mellitus is a modern global medical challenge with an estimated prevalence of 366 million patients in 2030 [6] .…”

“…The pathomechanism of NP has not yet been completely clarified, but the sensitization process is widely accepted as playing an important role. Hyperexcitability and sensitization in NP similar to migraine as a primary headache disorder involve changes in the peripheral nervous system and CNS [5,[13][14][15][16] . One of the key elements of the peripheral sensitization is the increased expression of voltage-gated sodium channels Na v 1.8 and Na v 1.9 on lesioned peripheral nerves, which are the sources of ectopic pain impulse generation.…”