Activation of peripheral and spinal histamine H3 receptors inhibits formalin-induced inflammation and nociception, respectively

Cannon, Keri E.; Leurs, Rob; Hough, Lindsay B.

doi:10.1016/j.pbb.2007.07.014

Cited by 47 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In rats, a moderate dose of thioperamide given alone (15 mg/kg i.p.) had no effect on either phase of formalin-induced flinching; this dose blocked immepip's antiflinching activity (Cannon et al, 2007b). However, a more recent study in rats reported dosedependent reductions in late-phase, formalin-induced flinching responses after systemic administration of the highly selective, potent H 3 inverse agonist 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridine carboxamide (GSK189254) (Hsieh et al, 2010b).…”

Section: Formalin-induced Nociceptionmentioning

confidence: 81%

“…In mice, oral BP 2-94 reduced both phases of formalin-induced licking and biting, but did not modify thermal (hot plate) responses . In a more recent rat study, systemic (subcutaneous) administration of the H 3 agonist immepip produced dose-dependent reductions (up to 70%) in both phases of formalin-induced flinching (Cannon et al, 2007b). These effects were mimicked by intrathecal immepip and blocked by systemic and intrathecal thioperamide.…”

Section: Formalin-induced Nociceptionmentioning

confidence: 90%

“…If this is correct, then the absence of H 3 Rs on C fibers in the skin (Fig. 1) and on small DRG neurons (Cannon et al, 2007a) seems to challenge the commonly held view that C-fiber activation evokes formalin-induced flinching (Cannon et al, 2007b). Instead, H 3 -containing peptidergic A␦ fibers (Cannon et al, 2007a) may be the critical elements for provoking this behavior (Cannon et al, 2007a,b).…”

Section: Formalin-induced Nociceptionmentioning

confidence: 96%

“…In the skin, activation of H 3 Rs on peptidergic A␦ fibers presumably suppresses neuropeptide release and attenuates inflammation-related edema (Ohkubo et al, 1995). In the spinal cord, activation of H 3 Rs reduces nociceptive responses elicited by low-intensity mechanical stimulation (Cannon et al, 2003) and proinflammatory agents such as formalin (Cannon et al, 2007b). Inhibition of transmitter release at the spinal terminations of these deep dermal fibers has been proposed to account for this antinociceptive activity.…”

Section: Formalin-induced Nociceptionmentioning

confidence: 99%

“…Inhibition of transmitter release at the spinal terminations of these deep dermal fibers has been proposed to account for this antinociceptive activity. Although the figure is based on immunohistochemical studies of the skin, DRG, and spinal cord, H 3 R activation is known to reduce inflammatory peptide release the heart (Imamura et al, 1996), lung (Delaunois et al, 1995), and dura mater (Dimitriadou et al, 1997 (Cannon et al, 2007b). Thus, studies in mice and rats with two different H 3 agonists Cannon et al, 2007b) suggest that inhibition of formalin flinching or licking is mediated by activation of spinal H 3 Rs on peptidergic afferent fibers.…”

Section: Formalin-induced Nociceptionmentioning

confidence: 99%

See 4 more Smart Citations

H₃ Receptors and Pain Modulation: Peripheral, Spinal, and Brain Interactions

Hough¹,

Rice²

2010

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Histamine H 3 receptors (H 3 Rs), distributed within 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 A␤ fibers, and on keratinocytes and Merkel cells, as well as on deep dermal, peptidergic A␦ fibers terminating on deep dermal blood vessels. Activation of H 3 Rs on the latter in the skin, heart, lung, and dura mater reduces calcitonin gene-related peptide 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 lowintensity mechanical stimuli and 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 periaqueductal gray (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. Histamine and PainHistamine, found throughout the body in both neuronal and non-neuronal sources, can modify pain transmission by actions at multiple receptors in the skin, spinal cord, and brain. Rapidly expanding information on the distribution and functions of H 3 receptors (H 3 Rs) and the recent development of new H 3 R ligands have heightened interest in the possible modulation of pain by H 3 R-acting drugs. The present article provides a short, integrative overview of relevant studies (for review see also Sander et al., 2008;Tiligada et al., 2009;Gemkow et al., 2009). Measuring Pain in the LaboratoryPain, which can be defined as the central representation of tissue-damaging stimuli with sensory-discriminative, motivational, and cognitive components (Besson and Chaouch, 1987), is readily understood by humans as a sensory experience. Ideally, evaluation of the pain-relieving properties of drugs should directly measure reductions in pain perception. Instead, assessment of analgesic drug action in nonverbal subjects relies heavily on measures of behavioral, often reflexive, responses. Because drugs can modify these responses (but not necessarily the underlying perceptions), results from pain testing in laboratory animals can be misleading. The present limitations of preclinical methodologies for identifying pain-relieving drugs have been discussed previously Vierck et al., 2008).Notwithstanding the limitations in state-of-the-art analgesic testing, many factors must be considered when evaluating

show abstract

Section: Formalin-induced Nociceptionmentioning

confidence: 81%

Section: Formalin-induced Nociceptionmentioning

confidence: 90%