Bidirectional Roles of TRPV1 in a Latent Sensitization Model of Myofascial Low Back Pain

TL;DR

This study explores the role of TRPV1 in a rat model of chronic low back pain, finding that TRPV1 contributes to pain sensitization but is not essential for its development.

Contribution

The study reveals TRPV1's bidirectional roles in spinal sensitization and its potential regulatory function in pain homeostasis.

Findings

TRPV1 is upregulated during manifest sensitization but not essential for developing mechanical hypersensitivity.

TRPV1−/− rats showed prolonged hypersensitivity after a single NGF injection, suggesting TRPV1's role in pain homeostasis.

Repeated NGF injections induced anxiety-like behavior and delayed remote hypersensitivity in both genotypes.

Abstract

Chronic primary low back pain (cpLBP) is a global health concern with poorly understood pathomechanisms, potentially involving spinal sensitization. The capsaicin receptor TRPV1 plays a crucial role in sensitization across pain models. This study employed a rat model of cpLBP induced by two nerve growth factor (NGF) injections into lumbar muscles to explore TRPV1's roles in NGF‐induced spinal sensitization.

Male wildtype (WT) and TRPV1−/− rats of both sexes (N = 10 each) underwent behavioural tests post NGF and vehicle injections. Tests included low back pressure pain thresholds (PPT), paw withdrawal thresholds (PWT), heat pain thresholds (HPT), and exploratory behaviour. Spinal TRPV1 expression after NGF injections was assessed in WT rats.

WT rats displayed latent local mechanical hypersensitivity after a single NGF injection, turning into manifest after the second, with presynaptic TRPV1 upregulation. TRPV1−/− rats showed pronounced local mechanical hypersensitivity after a single NGF injection, increasing after the second NGF injection. Repeated NGF injections led to anxiety‐like behaviour and delayed remote mechanical hypersensitivity in both genotypes.

TRPV1 is upregulated during manifest sensitization but is not essential for developing local or remote mechanical hypersensitivity. TRPV1−/− rats lacked early remission after a single NGF injection, suggesting TRPV1 may be involved in homeostatic maintenance rather than induction of spinal sensitization.

TRPV1 contributes to NGF‐induced sensitization but is not required for its development. These findings put TRPV1's potential as a therapeutic target for hyperalgesia into perspective and suggest a potential regulatory role in pain homeostasis.

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