The Contribution of TSLP Activation to Hyperalgesia in Dorsal Root Ganglia Neurons of a Rat.

Hung-Pei Tsai,Ying-Yi Lu,Chun-Ching Lu,Chieh-Hsin Wu

doi:10.3390/ijms23042012

Abstract

Peripheral nerve injury involves divergent alterations within dorsal root ganglia (DRG) neurons sensitized by persistent inflammation. Thymic stromal lymphopoietin (TSLP) production is crucial in the development of chronic inflammatory responses. Herein, we investigate the changes of TSLP expression in rats’ DRG neurons between injured and uninjured sides in the same rat. Linalyl acetate (LA) was served as a TSLP inhibitor and given intraperitoneally. Rats were assigned to be group of chronic constriction injury (CCI) of the sciatic nerve and the group of CCI of the sciatic nerve administrated with LA. Over 14 days, the rats were measured for paw withdrawal thresholds. DRGs were collected to assess morphological changes via immunofluorescence study. After receiving CCI, the rats rapidly developed mechanical hyperalgesia. TSLP expression at DRG, on the ipsilateral injured side, was consistent with changes in pain behaviors. TSLP appeared in nerve fibers with both small diameters and large diameters. Additionally, TSLP was expressed mostly in transient receptor potential vanilloid-1 (TRPV1)-positive nociceptive neurons. Administration with LA can attenuate the pain behaviors and expression of TSLP in DRG neurons, and in apoptotic neurons at the injured side, but not in the contra-lateral uninjured side. Overall, these results imply that altered expressions of TSLP in nociceptive DRG neurons contributed to mechanical hyperalgesia in a CCI rat model.

Highlights

Acting as a bridge between somatosensory information and the spinal cord, dorsal root ganglia (DRG) neurons transmit stimuli from peripheral nerve terminals to central nervous structures [1]
To assess whether the involvement of Thymic stromal lymphopoietin (TSLP) in sensory neurons differed between the ipsilateral injured side and the contralateral side, we examined the changes in TSLP expressed in rat DRGs
These results imply that mechanical hyperalgesia in the ipsilateral injured side of the nerve might be attributed to the changes in TSLP

Summary

Introduction

Acting as a bridge between somatosensory information and the spinal cord, dorsal root ganglia (DRG) neurons transmit stimuli from peripheral nerve terminals to central nervous structures [1]. In response to nerve injury, primary sensory neurons adapt their morphology and function to augment the peripheral sensitization and influence expression of nociceptors [3]. Prolonged inflammation from peripheral nerve injury induces the perception of pain though the activation or sensitization of nociceptors [5]. Neuropathic pain arises from lesions on somatosensory systems and manifests as paresthesia, dysesthesias, allodynia, hyperalgesia, and spontaneous unprovoked pain [6]. It usually occurs simultaneously with sensory loss and weakness [7,8,9] in the same afflicted nerve segment [10], which lacks efficient treatment options [11,12,13]. The blockade of both A-neurons and C-neurons can prevent mechanical allodynia effectively after nerve injury [19]

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Discussion

Conclusion