H3 Receptor Miniseries: H3 Receptors and Pain Modulation: Peripheral, Spinal and Brain Interactions.
Summary of "H3 Receptor Miniseries: H3 Receptors and Pain Modulation: Peripheral, Spinal and Brain Interactions."
Histamine H(3) receptors (H(3)Rs), distributed within in the brain, the spinal cord, and on specific types of primary sensory neurons, can modulate pain transmission by several mechanisms. In the skin, H(3)Rs are found on certain Aβ fibers, and on keratinocytes and Merkel cells, as well as on deep dermal, peptidergic Aδ fibers terminating on deep dermal blood vessels. Activation of H(3)Rs on the latter in the skin, heart, lung and dura mater reduces CGRP and substance P release, leading to anti-inflammatory (but not antinociceptive) actions. However, activation of H(3)Rs on the spinal terminals of these sensory fibers reduces nociceptive responding to low intensity mechanical stimuli, and to inflammatory stimuli such as formalin. These findings suggest that H(3)R agonists might be useful analgesics, but these drugs have not been tested in clinically-relevant pain models. Paradoxically, H(3) antagonists/ inverse agonists have also been reported to attenuate several types of pain responses, including phase II responses to formalin. In the periaquaductal gray (PAG, an important pain regulatory center), the H(3) inverse agonist thioperamide releases neuronal histamine and mimics histamine's biphasic modulatory effects in thermal nociceptive tests. Newer H(3) inverse agonists with potent, selective, and brain-penetrating properties show efficacy in several neuropathic and arthritis pain models, but the sites and mechanisms for these actions remain poorly understood.
1 Albany Medical College MC-136;
This article was published in the following journal.
Name: The Journal of pharmacology and experimental therapeutics
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20864501
- DOI: http://dx.doi.org/10.1124/jpet.110.171264
Medical and Biotech [MESH] Definitions
Peripheral Nervous System
The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.
The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)
Cell surface receptors that are specific for INTERLEUKIN-6. They are present on T-LYMPHOCYTES, mitogen-activated B-LYMPHOCYTES, and peripheral MONOCYTES. The receptors are heterodimers of the INTERLEUKIN-6 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130.
Peripheral cannabinoid receptors exert a powerful inhibitory control over pain initiation, but the endocannabinoid signal that normally engages this intrinsic analgesic mechanism is unknown. To addres...
Administration of hypertonic saline (HS) is an accepted model to study muscular pain. HS-induced nociceptive responses were tested in masseter, already described, and in two new pain models of spinall...
Neuropathic pain refers to chronic pain that results from injury to the nervous system. The mechanisms involved in neuropathic pain are complex and involve both peripheral and central phenomena. Altho...
Most of the modulating effects of cannabinoids on pain are through putative cannabinoid CB1 and CB2 receptors. However, the involvement of other receptors is also suggested. Cannabinoid compounds with...
Neuropathic pain is caused by the peripheral or central nervous system structure damage or dysfunction. VEGF is involved in nociception and inflammation. VEGF may target VEGF receptor-2 (VEGFR-2) on t...
Adenosine A1 and A2 receptors are widely distributed in the brain and spinal cord and represent a non-opiate target for pain management. Activated spinal A1 receptors inhibit sensory tran...
NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is ba...
Patients with peripheral neuropathy frequently exhibit treatment-refractory neuropathic pain. Although both peripheral and central determinants are recognized for the pathophysiological ba...
Patients with neuropathic pain exhibit hyperalgesia and allodynia. Although both peripheral and central determinants are recognized for the pathophysiological basis of neuropathic pain fol...
GSK239512 is being developed for the treatment of symptoms of cognitive impairment in many diseases. GSK239512 is a drug that binds to the Histamine 3 receptor (a protein) in the brain (r...