Background & Aims

The proalgesic transient receptor potential (TRP) ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons, has been implicated in various pain models in mice. However, evidence in rats indicates that TRPA1 conveys nociceptive signals elicited by channel agonists but not those associated with tissue inflammation or nerve injury. Here, in rats, we explored the TRPA1 role in mechanical allodynia associated with neurogenic inflammation and moderate (partial sciatic nerve ligation, pSNL) or severe (chronic constriction injury, CCI) sciatic nerve injury.

Methods

Acute nociception and mechanical hypersensitivity associated with neurogenic inflammation and sciatic nerve injury (pSNL and CCI) were investigated in rats with TRPA1 pharmacological antagonism or genetic silencing. TRPA1 presence and function was analyzed in cultured rat Schwann cells.

Results

Hind paw mechanical allodynia (HPMA), but not acute nociception, evoked by local injection of the TRP vanilloid 1 (TRPV1) agonist, capsaicin, or the TRPA1 agonist, allyl isothiocyanate, was mediated by calcitonin gene related peptide (CGRP) released from peripheral nerve terminals. CGRP-evoked HPMA was sustained by a reactive oxygen species (ROS)-dependent TRPA1 activation, probably in Schwann cells. HPMA evoked by pSNL, but not that evoked by CCI, was mediated by ROS and TRPA1 without the involvement of CGRP.

Conclusions

As found in mice, TRPA1 mediates mechanical allodynia associated with neurogenic inflammation and moderate nerve injury in rats. The channel implication in mechanical hypersensitivity following inflammation and partial nerve damage is a common rodent feature and might be explored in humans.

References

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Presenting Author

Gaetano De Siena

Poster Authors

Gaetano De Siena

Dott.

Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, F

Lead Author

E-mail

Francesco De Logu

Lead Author

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Lorenzo Doctor Landini

PhD

University of Florence

Lead Author

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Matilde Doctor Marini

PhD

University of Florence

Lead Author

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Daniel Doctor Araújo

PhD

University of Florence

Lead Author

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Martina Chieca PhD

Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, F

Lead Author

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Romina Nassini

University of Florence

Lead Author

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Topics

  • Models: Acute Pain