Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

Abstract

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions. (J Neurogastroenterol Motil 2015;21:147-158)

The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

“…Admittedly, in the cited studies, morphine did not prevent the reduced survivability of cells exposed to H 2 O 2 but did partially prevent lipid peroxidation and did not cause an increase in the level of sulfhydryl groups in the studied cells due to the H 2 O 2 exposure. Morphine is capable of activating the family of type µ opioid receptors (for morphine), λ (for ketocyclazocine), and κ (for diamorphine) [163]. Endogenous opioids are present in a number of structures of the central nervous system and spinal medulla.…”

<p>Dual-Acting Peripherally Restricted Delta/Kappa Opioid (CAV1001) Produces Antinociception in Animal Models of Sub-Acute and Chronic Pain</p>

“…Kappa-opioid agonists have previously been reported to be useful in various preclinical and clinical visceral pain models. 23,[42][43][44][45][46] Similarly, peripheral burn injury is associated with a dramatic inflammatory component. 47 Finally, although clinically the chronic widespread pain in fibromyalgia is related to a generalized increase in sensitivity to painful stimuli, and not considered to be primarily inflammatory, the condition may be in part a response to chronic low-grade inflammation, making it amenable to analgesics that take advantage of this persistent inflammatory response.…”

Cannabinoids, the Heart of the Matter

“…The cannabinoid (CB) receptors CB1 and CB2 are both members of the superfamily of metabotropic G‐protein‐coupled receptors (GPCRs), and have been cloned and identified in the human, rat, and mouse myocardium 40, 43, 48. The cannabinoid receptors are present in high abundance throughout the body where they, and their ligands, are involved in many important physiological functions and interactions with other neurotransmitters 31, 46…”

“…In addition, CB1 receptors also function in the peripheral nervous system: in vascular and cardiac tissue, adipocytes, liver, GI tract and uterus to regulate basic physiological mechanisms such as energy balance and reproduction 48, 50, 51. The CB1 receptor also has influence on memory and learning behavior, plays a role in addiction processes, and mediation of the psychoactive effect of Tetrahydrocannabinol (THC) 52, 53.…”