Normal and abnormal coding of somatosensory stimuli causing pain

Abstract

Noxious stimuli cause pain and pain arises from noxious stimuli… usually. Exceptions to these apparent truisms are the basis for clinically important problems and provide valuable insight into the neural code for pain. In this Perspective, we will discuss how painful sensations are encoded. We will argue that although primary somatosensory afferents are specialized (i.e. tuned to specific stimulus features), natural stimuli often activate >1 type of afferent. Manipulating co-activation patterns can alter perception, which argues against each type of afferent acting independently (as expected for strictly labeled lines) and suggests instead that signals conveyed by different types of afferents interact. Deciphering the central circuits that mediate those interactions is critical for explaining the generation and modulation of neural signals ultimately perceived as pain. The advent of genetic and optical dissection techniques promise to dramatically accelerate progress towards this goal, which will facilitate the rational design of future pain therapeutics.

Organization of the Thermal Grill Illusion by Spinal Segments

“…This evidence for cross‐modal interaction and convergence at the spinal level is incompatible with the classic specificity theory (ie, of labeled lines), and is driving a paradigm shift in the way somatosensation is currently viewed. The emerging “population coding model” suggests that temperature and pain perception arises from the joint activity across several neuronal populations, rather than depending on neural signals of specific labeled lines, with 1 dominant line associated with each specific sensory quality 39, 40, 41, 42. Our experiments are consistent with the view that TGI perception is largely influenced by the pooled activity of spinal neurons within 1 or 2 spinal segments.…”

Etiology and Pharmacology of Neuropathic Pain

“…Although lamina I contains interneurons for modulation and projection neurons for transmission of nociceptive information, lamina II contains mainly interneurons that project to lamina I. In spite of its importance, there is still very much that is unknown about dorsal horn circuitry and how it relates to the pathophysiology of chronic pain (Sandkuhler, 2009;Todd, 2010;Prescott et al, 2014;Peirs and Seal, 2016). Aspects of dorsal horn physiology and organization that are salient to pain etiology, drug development, and gabapentinoid action are described below.…”

Analysis of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa

“…The current understanding of long-term gabapentinoid action (Bauer et al 2009;Hendrich et al 2008;Patel et al 2013) has also yet to be integrated with what is known about nociceptive processing at both the spinal and peripheral level (Braz et al 2014;Prescott et al 2014;Todd 2010;Zeilhofer et al 2012). If gabapentinoids were to produce similar decreases in neurotransmitter release from all primary afferent terminals, they would produce an anesthetic rather than an antiallodynic effect.…”