Activation of spinal histamine H3 receptors inhibits mechanical nociception

Cannon, Keri E.; Nalwalk, Julia W.; Stadel, Rebecca; Ge, Pei; Lawson, D.; Silos-Santiago, I.; Hough, Lindsay B.

doi:10.1016/s0014-2999(03)01737-0

Cited by 57 publications

(60 citation statements)

References 52 publications

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“…A subsequent detailed evaluation with a wide variety of nociceptive stimuli in rats confirmed that the acute antinociceptive profile of H 3 agonists is both modality-specific (i.e., mechanical versus thermal) and intensity-specific (low versus high mechanical) (Cannon and Hough, 2005). Collectively, the studies show that low-intensity mechanical nociception is attenuated by activation of spinal H 3 Rs (Cannon et al, 2003;Cannon and Hough, 2005). Because 1) specific types of H 3 Rcontaining peripheral afferent fibers project to the dorsal horn, and 2) dorsal horn neurons have limited expression of H 3 R message (Héron et al, 2001) and H 3 RLI (Cannon et al, 2007a), it was suggested that the antinociceptive effects of intrathecal H 3 agonists are mediated by inhibition of transmitter release from afferent fibers in the spinal cord, a presynaptic effect (Cannon et al, 2003).…”

Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 72%

“…The opposite point also needs to be made: all H 3 R-related findings with these drugs cannot be dismissed a priori based only on H 4 properties. For example, immepip antinociception (discussed below) cannot be assumed to be caused by H 4 receptors (Gemkow et al, 2009) when the effect is mimicked by other H 3 agonists that lack H 4 affinity (e.g., RAMH; Lim et al, 2005), especially when the effect is abolished in H 3 R knockout mice (H 3 KO) mice (Cannon et al, 2003).…”

Section: Pharmacology Of H 3 R-acting Drugsmentioning

confidence: 99%

“…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%

“…In mice, immepip effectively attenuated mechanical nociception after intrathecal, but not subcutaneous, administration (Cannon et al, 2003). Because systemically administered immepip was effective against mechanical nociception in rats, Cannon et al (2003) suggested the possibility of a species difference in the spinal penetration by immepip, but several explanations seem possible for the discrepancy.…”

Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 99%

“…Because systemically administered immepip was effective against mechanical nociception in rats, Cannon et al (2003) suggested the possibility of a species difference in the spinal penetration by immepip, but several explanations seem possible for the discrepancy. A subsequent detailed evaluation with a wide variety of nociceptive stimuli in rats confirmed that the acute antinociceptive profile of H 3 agonists is both modality-specific (i.e., mechanical versus thermal) and intensity-specific (low versus high mechanical) (Cannon and Hough, 2005).…”

Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 99%

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

Hough¹,

Rice²

2010

J Pharmacol Exp Ther

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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

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Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 72%

Section: Pharmacology Of H 3 R-acting Drugsmentioning

confidence: 99%

Section: Formalin-induced Nociceptionmentioning

confidence: 99%

Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 99%

Section: Peripheral H 3 Rs and Inflammationmentioning

confidence: 99%

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

Hough¹,

Rice²

2010

J Pharmacol Exp Ther

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Neuropharmacology of Histamine in Brain

Faucard

Schwartz

2007

Handbook of Contemporary Neuropharmacology

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Histamine is an important neurotransmitter in brain. Histaminergic neurons emanating from the tuberomamillary nucleus in the hypothalamus project diffusely to the whole brain. Histamine acts via stimulation of three receptor subtypes and exerts essentially excitatory effects upon target neurons. The main function of histaminergic neurons is to trigger and maintain wakefulness and pro cognitive responses. Activation of histaminergic neurotransmission in brain is achieved via blockade of H3 receptors, and is currently explored as a treatment of wakefulness and cognitive deficits in several neurological and psychiatric diseases.

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Investigating the beneficial effect of aliskiren in attenuating neuropathic pain in diabetic Sprague‐Dawley rats

Alkhudhayri

Sajini

Alharbi

et al. 2020

Endocrino Diabet & Metabol

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Objectives Worldwide, diabetic neuropathy (DN) is a major complication of diabetes mellitus. The direct renin inhibitor aliskiren is recognized as a treatment for cardiovascular disease in diabetic patients, but little is known about its potential benefits in cases of diabetic neuropathy. Accordingly, we investigated the effects of aliskiren (ALIS) and gliclazide (GLZ) and their combination therapy on peripheral neuropathy in streptozotocin‐induced diabetic rats. Methods In total, 112 adult Sprague‐Dawley rats were used for this study. Diabetes was induced using streptozotocin (STZ), whereas the control group was treated with an equal volume of citrate buffer. The diabetic rats were divided randomly into six groups according to the proposed treatment regime: diabetic control (DC), gliclazide (GLZ), aliskiren (ALIS), ramipril (RAM), (GLZ + ALIS) and (GLZ + RAM). Behavioural responses to thermal (hot‐plate) and mechanical (tail‐pinch) pain were evaluated. After eight weeks of daily treatments, the animals were fasted and sacrificed. The blood samples were collected, with the serum separated and subjected to various biochemical and enzyme analyses so as to assess the effect of the treatments on diabetic peripheral neuropathy. Results After 8 weeks, aliskiren alone and in combination with gliclazide therapy had a significant effect (P < .001) in reducing blood glucose levels and showed increased hot‐plate and tail‐flick latencies compared with the diabetic control group. The threshold of mechanical hyperalgesia was also significantly elevated (P < .001). Conclusions/Interpretations These data suggest that either aliskerin alone or in combination with gliclazide can protect against the development and progression of diabetic neuropathy.

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Activation of spinal histamine H3 receptors inhibits mechanical nociception

Cited by 57 publications

References 52 publications

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

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

Neuropharmacology of Histamine in Brain

Investigating the beneficial effect of aliskiren in attenuating neuropathic pain in diabetic Sprague‐Dawley rats

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Activation of spinal histamine H3 receptors inhibits mechanical nociception

Cited by 57 publications

References 52 publications

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

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

Neuropharmacology of Histamine in Brain

Investigating the beneficial effect of aliskiren in attenuating neuropathic pain in diabetic Sprague‐Dawley rats

Contact Info

Product

Resources

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

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