Vivian Blechschmidt, Bastian Schlickenrieder, Jonathan R. Husk, Ulrich Hoheisel, Handan Mörz, Rolf‐Detlef Treede, Wolfgang Greffrath
ABSTRACT Introduction 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. Material and Methods 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. Results 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. Discussion 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. Significance Statement 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.