Direct Evidence for Neurogenic Inflammation and Its Prevention by Denervation and by Pretreatment With Capsaicin

Jancsó, N.; Jancsó-Gábor, A.; Szolcsányi, Janós

doi:10.1111/j.1476-5381.1967.tb01984.x

Cited by 807 publications

(395 citation statements)

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“…Capsaicin, the active ingredient of hot peppers, selectively stimulates and then desensitizes a subpopulation of C-fiber polymodal nociceptive and A␦ sensory nerve fibers that are classified as capsaicin-sensitive afferents (1,2). Capsaicin acts via transient receptor potential vanilloid 1 (TRPV1), which was cloned in 1997 and was formerly termed vanilloid receptor 1 (3).…”

Section: 05) In Trpv1mentioning

confidence: 99%

“…TRPV1 is a nonselective cation channel, which can be activated by noxious heat, protons, and vanilloids such as capsaicin, as well as a range of putative endogenous mediators (4,5). The acute stimulation of sensory nerves by capsaicin is associated with acute pain and neurogenic inflammation (1,2). Thermal nociceptive thresholds, observed after exposure to a hot plate or inflammatory insult in the paw, have been shown to be blunted in TRPV1-knockout mice, indicating the potential for TRPV1 in mediating inflammatory hyperalgesia (6,7).…”

Section: 05) In Trpv1mentioning

confidence: 99%

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Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Keeble¹,

Russell²,

Curtis³

et al. 2005

Arthritis & Rheumatism

154

117

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Objective. To investigate the endogenous involvement of transient receptor potential vanilloid 1 (TRPV1) in a model of knee joint inflammation in the mouse.Methods. Following characterization of wild-type (WT) and TRPV1-knockout mice, inflammation was induced via intraarticular (IA) injection of Freund's complete adjuvant (CFA). Knee swelling was assessed as diameter, and inflammatory heat hyperalgesia was determined using the Hargreaves technique, for up to 3 weeks. At 18 hours, acute hyperpermeability was measured with 125 I-albumin, and cytokines and myeloperoxidase activity, a marker of neutrophils, were assayed in synovial fluid extracts. The possibility that exogenous tumor necrosis factor ␣ (TNF␣) was involved in influencing TRPV1 activation was investigated in separate experiments.Results. Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNF␣ were found in WT mice 18 hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1 ؊/؊ mice, but leukocyte accumulation and TNF␣ levels were similar in WT and TRPV1 ؊/؊ mice. Knee swelling in response to CFA remained significantly higher for a longer period in WT mice compared with TRPV1 ؊/؊ mice, with thermal hyperalgesic sensitivity observed at 24 hours and at 1 week in WT, but not TRPV1 ؊/؊ , mice. Knee swelling was attenuated (P < 0.05) in TRPV1 ؊/؊ compared with WT mice 4 hours after IA administration of TNF␣.Conclusion. Our findings indicate that TRPV1 has a role in acute and chronic inflammation in the mouse knee joint. Thus, selective antagonism of TRPV1 should be considered as a potential target for treatment of acute and chronic joint inflammation.

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Section: 05) In Trpv1mentioning

confidence: 99%

Section: 05) In Trpv1mentioning

confidence: 99%

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Keeble¹,

Russell²,

Curtis³

et al. 2005

Arthritis & Rheumatism

154

117

View full text Add to dashboard Cite

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“…Because of the pioneering work of Jancso et al (1967) many in vivo and in vitro studies have shown Figure 6. Current versus time responses at Ϫ60 mV for 1 M olvanil, 1 M capsaicin, and 30 M GLNVA obtained in the same neuron using the methods described in Figure 5.…”

Section: Tachyphylaxismentioning

confidence: 99%

The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

Liu

Chen

et al. 1997

J. Neurosci.

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Capsaicin, the pungent ingredient in hot pepper, activates and subsequently desensitizes a subset of polymodal nociceptors. Because its initial application to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide (GLNVA) were synthesized to enhance its clinical use. To explore how these nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were performed on cultured rat trigeminal ganglion neurons.In neurons held at Ϫ60 mV, capsaicin, olvanil, and GLNVA were found to activate one or two kinetically distinct inward currents. Two inward currents were also activated when extracellular Ca 2ϩ was replaced with Ba 2ϩ and also when intracellular chloride was replaced by aspartate. The reversal potentials of the rapidly and slowly activating currents were 15.3 Ϯ 6 and Ϫ4.0 Ϯ 2.5 mV, respectively. These data provide strong evidence for subtypes of vanilloid receptors. One difference among these agonists is that, on average, the activation kinetics of the currents evoked by 1 M olvanil and 30 M GLNVA are considerably slower than those evoked by 1 M capsaicin. Measurements of the peak current, Ip, versus agonist concentration were fit to the Hill equation to yield values of the half maximal concentrations (K 1/2 ), and the Hill coefficients (n). For capsaicin, olvanil, and GLNVA, K 1/2 ϭ 0.68, 0.59, and 27.0 M; and n ϭ 1.38, 1.32, and 1.24, respectively.We propose that olvanil and GLNVA are nonpungent because they activate different subtypes of receptors and/or because of their activation kinetics (compared with capsaicin) are, on average, slower than the rate they inhibit action potentials from polymodal nociceptors. Key words: pain; taste; vanilloid receptors; pungent; olvanil; capsaicinCapsaicin, the pungent ingredient in chili pepper, produces pain and inflammation when placed on skin or mucus membranes (Holzer, 1991;Szolcanyi et al., 1991). These effects result from the activation of cation-selective channels in polymodal nociceptors causing peptides and transmitters to be released from their peripheral and central terminals. The selectivity of capsaicin for polymodal nociceptors, coupled with the fact that on repeated applications it produces a long-lasting desensitization of these neurons, has made it useful clinically as an anti-nociceptive and -inflammatory compound. a One disadvantage of using capsaicin clinically is that its initial contact with skin produces marked pain and inflammation that sometimes prevents continuance. To reduce these initial responses, protocols were developed in which the capsaicin concentration, the interstimulus interval, and the delivery vehicle were varied systematically (Craft and Porreca, 1992). Another approach was to synthesize analogs of capsaicin with properties that will not cause marked pain on the initial application. This latter approach has followed the pioneering structure activity work of Szolcsanyi and Jansco-Gabor (1975a,b), who found that analogs with longer acyl chains or with altered phenolic hydroxy groups were less pun...

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“…For example, injection of SP into the skin produces an intense vasodilatory response (15). This phenomenon is tied entirely to the integrity of the peripheral nervous system, since it can be suppressed by previous longterm treatment with capsaicin, which depletes the sensory neuropeptide reservoir (16). Furthermore, the peripheral sensory nerves produce not only vasodilation, but also a vasopermeability effect (16).…”

mentioning

confidence: 99%

Raynaud's phenomenon and scleroderma dysregulated neuroendothelial control of vascular tone

Kahaleh

Matucci‐Cerinic

1995

Arthritis & Rheumatism

103

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Direct Evidence for Neurogenic Inflammation and Its Prevention by Denervation and by Pretreatment With Capsaicin

Cited by 807 publications

References 18 publications

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

Raynaud's phenomenon and scleroderma dysregulated neuroendothelial control of vascular tone

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