| First Author | Chu WG | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 6 | Pages | 8526-8543 |
| PubMed ID | 32359120 | Mgi Jnum | J:311619 |
| Mgi Id | MGI:6713014 | Doi | 10.1096/fj.202000154RR |
| Citation | Chu WG, et al. (2020) TRPC1/4/5 channels contribute to morphine-induced analgesic tolerance and hyperalgesia by enhancing spinal synaptic potentiation and structural plasticity. FASEB J 34(6):8526-8543 |
| abstractText | Opioid analgesics remain the mainstay for managing intractable chronic pain, but their use is limited by detrimental side effects such as analgesic tolerance and hyperalgesia. Calcium-dependent synaptic plasticity is a key determinant in opiates tolerance and hyperalgesia. However, the exact substrates for this calcium-dependent synaptic plasticity in mediating these maladaptive processes are largely unknown. Canonical transient receptor potential 1, 4, and 5 (TRPC1, 4, 5) proteins assemble into heteromultimeric nonselective cation channels with high Ca(2+) permeability and influence various neuronal functions. However, whether and how TRPC1/4/5 channels contribute to the development of opiates tolerance and hyperalgesia remains elusive. Here, we show that TRPC1/4/5 channels contribute to the generation of morphine tolerance and hyperalgesia. Chronic morphine exposure leads to upregulation of TRPC1/4/5 channels in the spinal cord. Spinally expressed TRPC1, TPRC4, and TRPC5 are required for chronic morphine-induced synaptic long-term potentiation (LTP) as well as remodeling of synaptic spines in the dorsal horn, thereby orchestrating functional and structural plasticity during the course of morphine-induced hyperalgesia and tolerance. These effects are attributed to TRPC1/4/5-mediated Ca(2+) elevation in the spinal dorsal horn induced by chronic morphine treatment. This study identifies TRPC1/4/5 channels as a promising novel target to prevent the unwanted morphine tolerance and hyperalgesia. |
