Maladaptive changes in the homeostasis of AEA‑TRPV1/CB1R induces pain‑related hyperactivity of nociceptors after spinal cord injury

Spinal cord injury (SCI) can lead to chronic neuropathic pain due to overactive pain receptors (nociceptors). This study explores how an endocannabinoid called anandamide (AEA) and its receptors, TRPV1 and CB1R, contribute to this overactivity after SCI. The researchers found that after SCI, AEA levels increase, which parallels the hyperexcitability of nociceptors. TRPV1 and CB1R expression also increase at different times after SCI. High doses of AEA make naive DRG neurons more excitable through increased TRPV1 transcription. Activation of TRPV1 by AEA increases nociceptor excitability and calcium influx, while CB1R activation reduces excitability. This imbalance leads to a maladaptive state causing sustained pain. These findings offer potential targets for neuropathic pain treatment after SCI.

• 1
  SCI induces increased AEA content and hyperactivity in nociceptors, with the timing of SCI-induced hyperexcitability paralleling an increase in AEA content.
• 2
  TRPV1 and CB1R are upregulated in nociceptors following SCI, with TRPV1 primarily increased in neurons associated with chronic pain.
• 3
  High-dose AEA application on naive DRG can mimic the effects of SCI on nociceptors, and AEA induces hyperactivity in nociceptors via activation of TRPV1.