Differential involvement of TRPV1 receptors at the central and peripheral nerves in CFA-induced mechanical and thermal hyperalgesia

Kanai, Yoshihito; Hara, Tomokazu; Imai, Aki; Sakakibara, Ayano

doi:10.1211/jpp.59.5.0015

Cited by 68 publications

(60 citation statements)

References 28 publications

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“…On day 3 after the incision, SB366791 (150 µg) and/or HC-030031 (125 µg) or vehicle was subcutaneously administrated once into the incised sites in a volume of 25 µL using a 27-gauge needle. These doses of SB366791 and HC-030031 were determined from previous reports (Kanai et al 2007;Barabas and Stucky 2013). HHWT, CHWT, or MHWT was defined before and 30, 60, 90, and 120 min after the administration of SB366791, HC-030031, or vehicle as described above.…”

Section: Peripheral Administration Of Trpv1 or Trpa1 Antagonistmentioning

confidence: 99%

Involvement of TRPV1 and TRPA1 in Incisional Intraoral and Extraoral Pain

et al. 2015

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A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. Abstract Thermal and mechanical hypersensitivity in the injured region is a common complication. Although it is well known clinically that thermal and mechanical sensitivity of the oral mucosa is different from that of the skin, the mechanisms underlying injured pain of the oral mucosa remain poorly understood. The transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in primary afferent neurons are known to contribute to pathological pain. Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and mechanical hypersensitivity following oral mucosa or whisker pad skin incision. Strong heat and mechanical and cold hypersensitivity was caused in the buccal mucosa and whisker pad skin following incisions. On day 3 after the incisions, the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG) neurons innervating the buccal mucosa and whisker pad skin was significantly increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad skin, but not the buccal mucosa, was significantly increased. Administration of the TRPV1 antagonist, SB366791, to the incised site produced a significant suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin, as well as mechanical allodynia in the whisker pad skin. Administration of the TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as heat hyperalgesia in the whisker pad skin. These findings indicate that altered expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and mechanical hypersensitivity following the buccal mucosa and whisker pad skin incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed TG neurons in whisker pad skin-incised rats may contribute to the intracellular interactions of TRPV1 and TRPA1 associated with whisker pad skin incision, whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal mucosa-incised pain.

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Section: Peripheral Administration Of Trpv1 or Trpa1 Antagonistmentioning

confidence: 99%

Involvement of TRPV1 and TRPA1 in Incisional Intraoral and Extraoral Pain

et al. 2015

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“…We next evaluated whether peripheral inflammation triggers the release of endogenous linoleic acid metabolites in the spinal cord leading to TRPV1-mediated mechanical allodynia. We tested this hypothesis in the CFA model of inflammation since it is dependent upon spinal TRPV1 activity (6,8). Intraplantar injection of CFA resulted in the development of mechanical allodynia in the injected paw 24 h post injection (Fig.…”

Section: Depolarization Of the Spinal Cord Leads To Increased Release Ofmentioning

confidence: 99%

“…Interestingly, the systemic/spinal administration of TRPV1 antagonists blocks inflammation-induced heat hyperalgesia, as well as mechanical allodynia (5)(6). These findings were unexpected since TRPV1 is not activated by mechanical stimuli, suggesting that spinal TRPV1 activation leads to central sensitization to both thermal and mechanical stimuli (7)(8).…”

mentioning

confidence: 98%

Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia

Patwardhan¹,

Scotland

Akopian³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

198

191

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Transient receptor potential vanilloid 1 (TRPV1) plays a major role in hyperalgesia and allodynia and is expressed both in the peripheral and central nervous systems (CNS). However, few studies have evaluated mechanisms by which CNS TRPV1 mediates hyperalgesia and allodynia after injury. We hypothesized that activation of spinal cord systems releases endogenous TRPV1 agonists that evoke the development of mechanical allodynia by this receptor. Using in vitro superfusion, the depolarization of spinal cord triggered the release of oxidized linoleic acid metabolites, such as 9-hydroxyoctadecadienoic acid (9-HODE) that potently activated spinal TRPV1, leading to the development of mechanical allodynia. Subsequent calcium imaging and electrophysiology studies demonstrated that synthetic oxidized linoleic acid metabolites, including 9-HODE, 13-HODE, and 9 and 13-oxoODE, comprise a family of endogenous TRPV1 agonists. In vivo studies demonstrated that intrathecal application of these oxidized linoleic acid metabolites rapidly evokes mechanical allodynia. Finally, intrathecal neutralization of 9-and 13-HODE by antibodies blocks CFA-evoked mechanical allodynia. These data collectively reveal a mechanism by which an endogenous family of lipids activates TRPV1 in the spinal cord, leading to the development of inflammatory hyperalgesia. These findings may integrate many pain disorders and provide an approach for developing analgesic drugs.inflammation ͉ pain T ransient receptor potential vanilloid 1 (TRPV1) plays a pivotal role in many pain models, leading to the development of hyperalgesia and/or allodynia (1-2). TRPV1 is expressed in the peripheral as well as central nervous systems (CNS) including several areas involved in nociceptive transmission (3). Numerous studies have demonstrated that peripheral TRPV1 is activated by noxious heat and protons and is regulated by endogenous ligands (2), contributing to peripheral mechanisms of heat hyperalgesia (4). However, TRPV1 is also expressed in the CNS, where comparatively little is known about the role of this receptor in mediating central pain mechanisms.Recent studies have used TRPV1 antagonists to evaluate the role of CNS TRPV1 in inflammatory hyperalgesia. Interestingly, the systemic/spinal administration of TRPV1 antagonists blocks inflammation-induced heat hyperalgesia, as well as mechanical allodynia (5-6). These findings were unexpected since TRPV1 is not activated by mechanical stimuli, suggesting that spinal TRPV1 activation leads to central sensitization to both thermal and mechanical stimuli (7-8). Based upon these observations, we hypothesized that the afferent barrage resulting from peripheral tissue injury leads to generation of endogenous TRPV1 ligands in the spinal cord that activate TRPV1 in the CNS resulting in central sensitization. Results Depolarization of Spinal Cord Results in the Release of EndogenousTRPV1 Ligands. To evaluate the hypothesis that endogenous TRPV1 agonists are released from spinal cord neurons, freshly isolated male rat spinal cords w...

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“…This receptor can be activated by noxious heat (Ͼ43°C), extracellular acidification, various lipids, and capsaicin (Caterina et al, 1997;Tominaga and Tominaga, 2005). Several studies demonstrated that TRP channel functions are modulated during inflammation (Ji et al, 2002;Kanai et al, 2007;De Schepper et al, 2008). One of the representations of such a modulation is an inflammatory-mediated heat hyperalgesia (Zhuang et al, 2004;Breese et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor Contribution via Transient Receptor Potential Vanilloid 1 to Ectopic Orofacial Pain

Shinoda¹,

Asano²,

Omagari³

et al. 2011

J. Neurosci.

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It is well known that oral inflammation causes tenderness in temporomandibular joints or masseter muscles. The exact mechanism of such an orofacial ectopic hyperalgesia remains unclear. Here, we investigated the functional significance of interaction of nerve growth factor (NGF) and transient receptor potential vanilloid 1 (TRPV1) in relation to heat hyperalgesia in the whisker pad skin caused by complete Freund's adjuvant (CFA) injection into the lower lip. CFA injection induced heat hyperalgesia of the ipsilateral whisker pad skin. Moreover, it leads to enhancement of spontaneous activity and heat responses in trigeminal ganglion (TG) neurons that was elicited by heat stimulation of the whisker pad skin. The heat hyperalgesia was dose-dependently reversed by intraperitoneal TRPV1 antagonist administration, also diminished by neutralizing anti-NGF antibody administration into the lower lip and intraganglionic administration of K252a, a tyrosine kinase receptor inhibitor. Nerve fibers in bundle of mandibular nerve and TG neurons that innervates the whisker pad skin and lower lip both expressed labeled NGF, which was administrated into the lower lip. Moreover, the NGF concentrations in ophthalmic-maxillary and mandibular divisions of the TG increased after CFA injection into the lower lip. The number of TRPV1-positive neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip, and this increase was annulled by anti-NGF administration. The present findings suggest that inflammation in the lower lip induces release of NGF that regulates TRPV1 expression in TG neurons. This TRPV1 overexpression may underlie ectopic heat hyperalgesia in the whisker pad skin.

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Differential involvement of TRPV1 receptors at the central and peripheral nerves in CFA-induced mechanical and thermal hyperalgesia

Cited by 68 publications

References 28 publications

Involvement of TRPV1 and TRPA1 in Incisional Intraoral and Extraoral Pain

Involvement of TRPV1 and TRPA1 in Incisional Intraoral and Extraoral Pain

Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia

Nerve Growth Factor Contribution via Transient Receptor Potential Vanilloid 1 to Ectopic Orofacial Pain

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