Rab27a Contributes to the Processing of Inflammatory Pain in Mice.

Tilman Gross,Wiebke Kallenborn-Gerhardt,Gerd Geisslinger,Katharina M J Syhr,Miguel C Seabra,Gesine Wack,Tanya Tolmachova,Ellen Niederberger,Achim Schmidtko

doi:10.3390/cells9061488

Tilman Gross, Wiebke Kallenborn-Gerhardt + Show 7 more

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https://doi.org/10.3390/cells9061488

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Abstract

Tissue injury and inflammation may result in chronic pain, a severe debilitating disease that is associated with great impairment of quality of life. An increasing body of evidence indicates that members of the Rab family of small GTPases contribute to pain processing; however, their specific functions remain poorly understood. Here, we found using immunofluorescence staining and in situ hybridization that the small GTPase Rab27a is highly expressed in sensory neurons and in the superficial dorsal horn of the spinal cord of mice. Rab27a mutant mice, which carry a single-nucleotide missense mutation of Rab27a leading to the expression of a nonfunctional protein, show reduced mechanical hyperalgesia and spontaneous pain behavior in inflammatory pain models, while their responses to acute noxious mechanical and thermal stimuli is not affected. Our study uncovers a previously unrecognized function of Rab27a in the processing of persistent inflammatory pain in mice.

Highlights

Chronic pain is a major source of suffering and one of the most frequent causes for patients to seek medical care [1]
We assessed the behavior of Rab27aash/ash mice in a second model of inflammatory pain
Rab27a is highly expressed in nociceptive C fiber neurons and their terminals in the superficial dorsal horn of the spinal cord

Summary

Introduction

Chronic pain is a major source of suffering and one of the most frequent causes for patients to seek medical care [1]. It is important to elucidate molecular mechanisms of nociceptive processing in order to develop novel strategies for chronic pain treatment [2,3,4]. Accumulating evidence suggests that various Rab proteins contribute to pain signaling, but their specific functions remain poorly understood. Rab proteins belong to the Ras superfamily of small guanosine triphosphatases (GTPases). As monomeric G-proteins they exist in a GTP and a GDP-bound state and their activity is regulated by guanosine nucleotide dissociation inhibitors and guanine nucleotide exchange factors (for review see [5]). More than 60 Rab proteins have been identified, which are involved in basic cellular processes such as cellular trafficking, vesicular trafficking

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