Nociception, pain, and antinociception: current concepts

Abstract

The physiology of nociception involves a complex interaction of peripheral and central nervous system (CNS) structures, extending from the skin, the viscera and the musculoskeletal tissues to the cerebral cortex. The pathophysiology of chronic pain shows alterations of normal physiological pathways, giving rise to hyperalgesia or allodynia. After integration in the spinal cord, nociceptive information is transferred to thalamic structures before it reaches the somatosensory cortex. Each of these levels of the CNS contain modulatory mechanisms. The two most important systems in modulating nociception and antinociception, the N-methyl-D-aspartate (NMDA) and opioid receptor system, show a close distribution pattern in nearly all CNS regions, and activation of NMDA receptors has been found to contribute to the hyperalgesia associated with nerve injury or inflammation. Apart from substance P (SP), the major facilitatory effect in nociception is exerted by glutamate as the natural activator of NMDA receptors. Stimulation of ionotropic NMDA receptors causes intraneuronal elevation of Ca2+ which stimulates nitric oxide synthase (NOS) and the production of nitric oxide (NO). NO as a gaseous molecule diffuses out from the neuron and by action on guanylyl cyclase, NO stimulates in neighboring neurons the formation of cGMP. Depending on the expression of cGMP-controlled ion channels in target neurons, NO may act excitatory or inhibitory. NO has been implicated in the development of hyperexcitability, resulting in hyperalgesia or allodynia, by increasing nociceptive transmitters at their central terminals. Among the three subtypes of opioid receptors, mu- and delta-receptors either inhibit or potentiate NMDA receptor-mediated events, while kappa opioids antagonize NMDA receptor-mediated activity. Recently, CRH has been found to act at all levels of the neuraxis to produce analgesia. Modulation of nociception occurs at all levels of the neuraxis, thus, eliciting the multidimensional experience of pain involving sensory-discriminative, affective-motivational, cognitive and locomotor components.

Assessment of Mechanisms Involved in Antinociception Caused by Myrsinoic Acid B

“…The L-arginine/nitric oxide pathways are involved in several models of nociception. 11,14) Then we demonstrated across the results that the L-arginine-nitric oxide pathway is likely to be involved in antinociception caused by AMB. This conclusion is drawn from the fact that pre-treatment of the mice with the nitric oxide synthase (NOS) substrate L-arginine, at a dose that produced no significant effect on acetic acid-induced pain, significantly reversed the antinociception caused by both AMB and L-NOARG (a known nitric oxide inhibitor).…”

The impact of morphine after a spinal cord injury

“…Limb withdrawal from mechanical stimulation can be elicited after spinal transection, suggesting that the change in tactile reactivity reported above could involve an intraspinal modification related to the sensitization of spinal neurons [30,31,32]. Vocalization to shock provides a supraspinal measure of sensory function and it revealed a different pattern of results; both prior shock and morphine treatment increased vocalization thresholds, suggesting both treatments increased the loss of sensory fibers.…”

Potential Muscle Biomarkers of Chronic Myalgia in Humans - A Systematic Review of Microdialysis Studies

“…BKN and KAL are kinins -a group of structurally related 9-11 amino acid peptides that are produced by kallikrein-mediated enzymatic cleavage of kininogen (Coutaux et al, 2005;Riedel & Neeck, 2001;Wang et al, 2006). Kinins mediate their effects via two different G protein coupled receptors, B 1 and B 2 , that provoke an increase in intracellular Ca 2+ (Meyer et al, 2006;Zubakova et al, 2008).…”