Extending the Therapeutic Scope for the Treatment of Neuropathic Pain with Topical Analgesics

Neuropathic pain is defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” [1]. Peripheral nerve damage causes the release of pro-inflammatory mediators (including interleukin-1β, tumor necrosis factor-α, bradykinin, substance P, calcitonin gene-related peptide, nerve growth factor, and prostaglandins) contributing to the ‘inflammatory soup’[2] The inflammatory response has adaptive functions enabling nerve repair [2]. On the other hand, these mediators have the undesired effect of sensitizing and stimulating nociceptors, leading to neuropathic pain [2]. The intensity of neuropathic pain progressively increases throughout the day [3]. This circadian cycle of neuropathic pain might be due to fluctuation of neurotransmitters and endocrine hormones, as well as repeated somatic stimulation and physical activity [3]. Allodynia (a potential characteristic of neuropathic pain) can exhibit temporal summation [3]. The fact that neuropathic pain often restricts walking and mobility, implies that physical activity evokes or exacerbates neuropathic pain [3]. Thus sensitization and stimulation of the peripheral nerve seem to play an important role in the aggravation throughout the day.