Potentiation of Nociceptive Responses to Low pH Injections in Humans by Prostaglandin E2

Rukwied, Roman; Chizh, Boris A.; Lorenz, U.; Obreja, Otilia; Mărgărit, Simona; Schley, Marcus; Schmelz, Martin

doi:10.1016/j.jpain.2006.12.004

Cited by 37 publications

(33 citation statements)

References 55 publications

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“…For example, injection of inflammatory mediators including prostaglandin E2 increases the acid-induced pain ratings in humans Birklein et al, 2000;Chen et al, 2006;Rukwied et al, 2007). In addition, acidic solution injected into the forearm skin or muscle resulted in higher pain ratings in patients with complex regional pain syndrome than the control subjects (Birklein et al, 2000) indicating that the presence of inflammation increases responses to tissue acidity.…”

Section: Discussionmentioning

confidence: 99%

Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression

Ambalavanar

Yallampalli

et al. 2007

Neuroscience

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Craniofacial muscle pain including muscular temporomandibular disorders accounts for a substantial portion of all pain perceived in the head and neck region. In spite of its high clinical prevalence, the mechanisms of chronic craniofacial muscle pain are not well understood. Injection of acidic saline into rodent hindlimb muscles produces pathologies which resemble muscular pathologies in chronic pain patients. Here we investigated whether analogous transformations occur following repeated injections of acidic saline into the rat masseter muscle. Injection of acidic saline (pH 4) into the masseter muscle transiently lowered intramuscular pH to levels comparable to those reported for rodent hindlimb muscles. Nevertheless, repeated unilateral or bilateral injections of acidic saline (pH 4) into the masseter muscle failed to alter nociceptive behavioral responses as occurs in the hindlimb. Changing the pH of injected saline to pH 3.0 or 5.0 also did not evoke nocifensive behavior. ASIC3 receptors, which are implicated in transformations following acidification of hindlimb muscles, were found on trigeminal ganglion muscle afferent neurons via combined neuronal tracing and immunocytochemistry. In contrast to the acidic saline, injection of complete Freund's adjuvant (CFA) into the masseter muscle induced mechanical allodynia for three weeks, thermal hyperalgesia for one week and an increase in the number of CGRP-immunoreactive muscle afferent neurons in the trigeminal ganglion. Although pH may alter CGRP release in primary afferent neurons, the number of CGRP-muscle afferent neurons did not change following intramuscular injection of acidic saline. Further, there was no change in ganglionic iCGRP levels at one, four or twelve days after intramuscular injection of acidic saline. While these findings extend our earlier reports that CFAinduced muscle inflammation results in behavioral and neuropeptide changes they further suggest that intramuscular acidification in craniofacial muscle evokes different responses than in hindlimb muscle and imply that disparate proton sensing mechanisms underlie these discrepancies. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 9. Published in final edited form as:Neuroscience. 2007 November 9; 149(3): 650-659. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptFifteen percent of the American population suffers from chronic musculoskeletal pain, placing a substantial burden on the health care system (Magni et al., 1993;...

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Section: Discussionmentioning

confidence: 99%

Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression

Ambalavanar

Yallampalli

et al. 2007

Neuroscience

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“…PGE 2 injected into the tail of rhesus monkeys also induced heat hyperalgesia with slight differences between females and males as well as between follicular and luteal phase females showing a minor role for sex and gonadal hormone levels (531). In humans, intradermal injection of PGE 2 led to heat hyperalgesia measured as a reduced heat pain threshold (618). However, PGE 2 may increase local skin temperature which lowers heat pain threshold, an effect also reported from the rat tail (for review, see Ref.…”

Section: Prostanoid-induced Sensitization To Heat Stimulimentioning

confidence: 96%

“…However, exogenously introduced PGE 2 is a surprisingly poor algogenic agent, at least in human skin. High concentrations caused a minimal heat hyperalgesia, lowering the threshold by Ͻ1°C, and a marginal increase in painfulness of mild-acid injections; the sensation induced by 100 M PGE 2 was one of mild itch, not pain, which corresponded to a moderate excitatory effect on few histamine-sensitive C-fibers in human microneurography recordings (532,618,642). On the other hand, the pain induced by intradermal acid buffer infusion or by topical (transdermal) capsaicin was most effectively reduced by either topical or systemic administration of acetylsalicylic acid and other prostaglandin synthesis inhibitors (640,671,672).…”

Section: Effects Of Inflammatory Mediators On Peripheral Nociceptorsmentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

244

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…However, it has been also suggested that species differences and co-expression of heteromultimeric ASICs complexes contribute to various pH sensitivity (Wemmie et al, 2006;Diochot et al, 2007). In addition, during inflammatory conditions, interactions between prostanoids and TRPV1 could modify the pH threshold values of ASICs (Agopyan et al, 2003;Gu and Lee, 2006;Cushman et al, 2007;Rukwied et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Acid-induced modulation of airway basal tone and contractility: Role of acid-sensing ion channels (ASICs) and TRPV1 receptor

et al. 2007

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Potentiation of Nociceptive Responses to Low pH Injections in Humans by Prostaglandin E2

Cited by 37 publications

References 55 publications

Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression

Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Acid-induced modulation of airway basal tone and contractility: Role of acid-sensing ion channels (ASICs) and TRPV1 receptor

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