Inflammation‐induced hyperexcitability of nociceptive gastrointestinal DRG neurones: the role of voltage‐gated ion channels

Abstract

Gastrointestinal (GI) inflammation modulates the intrinsic properties of nociceptive dorsal root ganglia neurones, which innervate the GI tract and these changes are important in the genesis of abdominal pain and visceral hyperalgesia neurones exhibit hyperexcitability characterized by a decreased threshold for activation and increased firing rate, and changes in voltages-gated Na(+) and K(+) channels play a major role in this plasticity. This review highlights emerging evidence that specific subsets of channels and signalling pathways are involved and their potential to provide novel selective therapeutics targets for the treatment of abdominal pain.

Periodate Oxidized ATP (oATP) Reduces Hyperalgesia in Mice: Involvement of P2X7 Receptors and Implications for Therapy

“…The visceral pain is typically present in many important gastroenteric diseases. In fact the nociceptive dorsal root ganglia neurons, which innervate the gastrointestinal tract, due to the inflammation-induced hyperexcitability, are involved in the genesis of abdominal pain (24). In addition, neurogenic inflammation is a possible amplifier of the noxious signal from visceral organs such as the pancreas (25).…”

Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats

“…The peripheral sensitization involves an increase in excitability of primary afferent nociceptors, which convey peripheral stimuli into action potentials (APs) that propagate to the central nervous system (8,11). Sensitization of primary sensory neurons is maintained by a number of ion channels such as transient receptor potential channels (34), P2X3 receptors (43), and voltage-gated Na ϩ , K ϩ , and Ca 2ϩ channels (7,28,45). Both the suppression of K ϩ currents and promotion of Na ϩ currents appear to contribute to peripheral sensitization in different pain models (6,7,36,46).…”

“…Sensitization of primary sensory neurons is maintained by a number of ion channels such as transient receptor potential channels (34), P2X3 receptors (43), and voltage-gated Na ϩ , K ϩ , and Ca 2ϩ channels (7,28,45). Both the suppression of K ϩ currents and promotion of Na ϩ currents appear to contribute to peripheral sensitization in different pain models (6,7,36,46). Luo et al (31) recently reported that neonatal maternal separation led to a significant reduction in I K current density and expression of K V 1.2 subunit of colonspecific dorsal root ganglion (DRG) neurons in adult rats, indicating a role for voltage-gated potassium channels (VGPCs) in NMD-induced visceral hypersensitivity.…”

Visceral antinociceptive and proinflammatory effects of proteinase activated receptor-4 and its role in the pathogenesis of ulcerative

“…In both studies distensions were conducted in the rectum, where CD patients had no inflammation, and UC patients had no or only mild inflammation. Intestinal inflammation is generally associated to increased visceral sensitivity, as mucosal immunal cells are able to release algogenic molecules in the proximity of nerve endings (10,21,31), and mediators released from non-immune cells have also been proposed to play a role in sensitizing afferent neurons (10,12,39). However, no inflammatory mediator has been found so far which can explain the rectal hyposensitivity observed in IBD patients.…”

“…In contrast in colitis, a vaste amount of inflammatory mediators are released to the colonic wall, such as bradikinin (27) or prostaglandins (36), which can trigger higher response to colonic distension. Inflammatory mediators may sensitize colonic afferents to enhance firing in response to painful stimuli (12). A study on rat spinal neurons showed a significantly increased activity to CRD in acute colonic inflammation (71).…”