Pain Behaviors Produced by Capsaicin: Influence of Inflammatory Mediators and Nerve Injury

Sawynok, Jana; Reid, Allison; Meisner, Jason G.

doi:10.1016/j.jpain.2005.09.013

Cited by 29 publications

(22 citation statements)

References 53 publications

(54 reference statements)

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“…These results are consistent with the phenotypes of mice lacking either functional TRPM8 channels or intact TRPM8 + afferent neurons as these animals have deficits only in cold sensitivity 23,25,27,43 . The ability of cold to induce to QX-314 nerve block, particularly innocuous cool (20 °C) is clinically advantageous over agonists such as capsaicin or WS-12 as these agents instantly activate their respective channels, causing irritation and pain 26,44 . Innocuous temperatures would be perceived as pleasant and be more amenable to long lasting stimulation for more prolonged uptake of the nerve blocker in a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Selective cold pain inhibition by targeted block of TRPM8-expressing neurons with quaternary lidocaine derivative QX-314

2018

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Treatment of pain with local anesthetics leads to an unfavorable decrease in general sensory acuity due to their indiscriminate block of both pain sensing (nociceptors) and non-pain sensing nerves. However, the cell impermeant lidocaine derivative QX-314 can be selectively targeted to only nociceptors by permeation through ligand-gated cation channels. Here we show that localized injection of QX-314 with agonists for the menthol receptor TRPM8 specifically blocks cold-evoked behaviors in mice, including cold allodynia and hyperalgesia. Remarkably, cooling stimuli also promotes QX-314-mediated inhibition of cold behaviors, and can be used to block cold allodynia, while retaining relatively normal cold sensation. The effects of both agonist and thermally evoked uptake of QX-314 are TRPM8-dependent, results demonstrating an effective approach to treat localized cold pain without altering general somatosensation.

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Section: Discussionmentioning

confidence: 99%

Selective cold pain inhibition by targeted block of TRPM8-expressing neurons with quaternary lidocaine derivative QX-314

2018

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“…PGE 2 augmented CGRP release induced by bradykinin in the bovine dental pulp and isolated rat skin (29,240). PGE 2 applied intraplantarly augmented the capsaicin-evoked nocifensive reaction in the rat hindpaw (634). In anesthetized rats, PGE 2 increased the discharge activity of single pulmonary C-fibers evoked by capsaicin, lactate, or adenosine (287).…”

Section: Effects Of Inflammatory Mediators On Peripheral Nociceptorsmentioning

confidence: 99%

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

Pethő

Reeh

2012

Physiological Reviews

240

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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“…Subcutaneous capsaicin binds to and activates TRPV1, which gives rise to pain-like behaviors such as licking, biting, and flinching (Sawynok et al, 2006). In this study, we evaluated capsaicininduced pain score in a similar manner as that used for the formalin test.…”

Section: Inhibition Of Capsaicin-induced Pain Behaviors Following Actmentioning

confidence: 99%

Activation of Spinal μ- and δ-Opioid Receptors Potently Inhibits Substance P Release Induced by Peripheral Noxious Stimuli

Beaudry¹,

Dubois²,

Gendron³

2011

J. Neurosci.

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Over the past few years, ␦-opioid receptors (DOPRs) and -opioid receptors (MOPRs) have been shown to interact with each other. We have previously seen that expression of MOPR is essential for morphine and inflammation to potentiate the analgesic properties of selective DOPR agonists. In vivo, it is not clear whether MOPRs and DOPRs are expressed in the same neurons. Indeed, it was recently proposed that these receptors are segregated in different populations of nociceptors, with MOPRs and DOPRs expressed by peptidergic and nonpeptidergic fibers, respectively. In the present study, the role and the effects of DOPR-and MOPR-selective agonists in two different pain models were compared. Using preprotachykinin A knock-out mice, we first confirmed that substance P partly mediates intraplantar formalin-and capsaicin-induced pain behaviors. These mice had a significant reduction in pain behavior compared with wild-type mice. We then measured the effects of intrathecal deltorphin II (DOPR agonist) and DAMGO (MOPR agonist) on pain-like behavior, neuronal activation, and substance P release following formalin and capsaicin injection. We found that both agonists were able to decrease formalin-and capsaicin-induced pain, an effect that was correlated with a reduction in the number of c-fos-positive neurons in the superficial laminae of the lumbar spinal cord. Finally, visualization of NK 1 (neurokinin 1) receptor internalization revealed that DOPR and MOPR activation strongly reduced formalin-and capsaicin-induced substance P release via direct action on primary afferent fibers. Together, our results indicate that functional MOPRs and DOPRs are both expressed by peptidergic nociceptors.

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Pain Behaviors Produced by Capsaicin: Influence of Inflammatory Mediators and Nerve Injury

Cited by 29 publications

References 53 publications

Selective cold pain inhibition by targeted block of TRPM8-expressing neurons with quaternary lidocaine derivative QX-314

Selective cold pain inhibition by targeted block of TRPM8-expressing neurons with quaternary lidocaine derivative QX-314

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

Activation of Spinal μ- and δ-Opioid Receptors Potently Inhibits Substance P Release Induced by Peripheral Noxious Stimuli

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