Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on mechanosensitive group IV muscle afferents in the rat

Hoheisel, Ulrich; Unger, Thomas; Mense, Siegfried

doi:10.1016/j.pain.2004.12.020

Cited by 151 publications

(100 citation statements)

References 51 publications

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“…The reason Mann et al (2006) did not see any effect with rat NGF is not clear. Hoheisel et al (2005) showed excitation by NGF in high-threshold mechanoreceptors, but failed to show mechanical sensitization. The observation period (up to 15 min) might have been too short to detect sensitization.…”

Section: Discussionmentioning

confidence: 95%

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

Murase

Terazawa²,

Queme³

et al. 2010

J. Neurosci.

160

183

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Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after ϳ1 d. Using B 2 bradykinin receptor antagonist HOE 140, we show here that bradykinin released during exercise plays a pivotal role in triggering the process that leads to muscular mechanical hyperalgesia. HOE 140 completely suppressed the development of muscular mechanical hyperalgesia when injected before LC, but when injected 2 d after LC failed to reverse mechanical hyperalgesia that had already developed. B 1 antagonist was ineffective, regardless of the timing of its injection. Upregulation of nerve growth factor (NGF) mRNA and protein occurred in exercised muscle over a comparable time course (12 h to 2 d after LC) for muscle mechanical hyperalgesia. Antibodies to NGF injected intramuscularly 2 d after exercise reversed muscle mechanical hyperalgesia. HOE 140 inhibited the upregulation of NGF. In contrast, shortening contraction or stretching induced neither mechanical hyperalgesia nor NGF upregulation. Bradykinin together with shortening contraction, but not bradykinin alone, reproduced lasting mechanical hyperalgesia. We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10 -20 min. Thus, NGF upregulation through activation of B 2 bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.

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Section: Discussionmentioning

confidence: 95%

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

Murase

Terazawa²,

Queme³

et al. 2010

J. Neurosci.

160

183

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“…The human psychophysical data is clear about the fact that acute elevation of NGF in muscle, as opposed to skin, can produce a rapid sensitization, but even here there is little data to indicate why this may be the case. In one study in rats, NGF was injected directly into the muscle and led to an apparent activation of C-fibers afferents in the muscle, but did not lead to an acute sensitization of muscle C-fibers to mechanical stimuli (Hoheisel et al, 2005). In common with the innervation of the viscera (McMahon and Koltzenburg, 1990), normal skeletal muscle is innervated by a large number of C-fibers that insensitive to mechanical stimuli (Jankowski et al, 2013).…”

Section: Recordings From Nociceptors Innervating Uv-b Sensitized Skinmentioning

confidence: 99%

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Lewin

Lechner

Smith

2014

Handbook of Experimental Pharmacology

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Nerve growth factor (NGF) is central to the development and functional regulation of sensory neurons that signal the first events that lead to pain. These sensory neurons, called nociceptors, require NGF in the early embryo to survive and also for their functional maturation. The long road from the discovery of NGF and its roles during development to the realization that NGF plays a major role in the pathophysiology of inflammatory pain will be reviewed. In particular, we will discuss the various signaling events initiated by NGF that lead to long lasting thermal and mechanical hyperalgesia in animals and in man. It has been realized relatively recently that humanized, function blocking antibodies directed against NGF show remarkably analgesic potency in human clinical trials for painful conditions as varied as osteoarthritis, lower back pain and interstitial cystitis. Thus, anti-NGF medication has the potential to make a major impact on day-to-day pain treatment in the near future. It is therefore all the more important to understand the precise pathways and mechanisms that are controlled by NGF to initiate and sustain mechanical and thermal hyperalgesia. Recent work suggests that NGF-dependent regulation of the mechanosensory properties of sensory neurons that signal mechanical pain may open new mechanistic avenues to refine and exploit relevant molecular targets for novel analgesics.

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“…As a model of myofascial widespread pain, we used repeated intramuscular injections of nerve growth factor (NGF), which is known to be associated with fascia and muscle pain (Hoheisel et al, 2005(Hoheisel et al, , 2007Hayashi et al, 2011;Deising et al, 2012) and to induce long-lasting hyperalgesia in animals (Hoheisel et al, 2007;Mills et al, 2013) and humans (Herren-Gerber et al, 2011;Deising et al, 2012;Hayashi et al, 2013). Antibodies against NGF are currently under investigation for pain treatment in humans (Cattaneo, 2010;Pfizer, 2012).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

Lomazzo

Bîndilă

Remmers

et al. 2014

Neuropsychopharmacol

Self Cite

122

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The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We found that CUS increased anxiety-and depression-like behavior and enhanced basal nociception in mice. When co-applied with repeated NGF injections, CUS elicited a sustained long-lasting widespread hyperalgesia. In order to evaluate a potential therapeutic strategy for the treatment of chronic pain associated with stress, we hypothesized that the endocannabinoid system (ECS) may represent a target signaling system. We found that URB597, an inhibitor of the anandamidedegrading enzyme fatty acid amide hydrolase (FAAH), and JZL184, an inhibitor of the 2-arachidonoyl glycerol-degrading enzyme monoacylglycerol lipase (MAGL), increased eCB levels in the brain and periphery and were both effective in reducing CUS-induced anxiety measured by the light-dark test and CUS-induced thermal hyperalgesia. Remarkably, the long-lasting widespread hyperalgesia induced by combining CUS and NGF was effectively reduced by URB597, but not by JZL184. Simultaneous inhibition of FAAH and MAGL did not improve the overall therapeutic response. Therefore, our findings indicate that enhancement of anandamide signaling with URB597 is a promising pharmacological approach for the alleviation of chronic widespread nociception in stress-exposed mice, and thus, it could represent a potential treatment strategy for chronic pain associated with neuropsychiatric disorders in humans.

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Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on mechanosensitive group IV muscle afferents in the rat

Cited by 151 publications

References 51 publications

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

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