Body “pain” is treated in the brain: A new therapeutic strategy targeting pain-causing neuronal circuits

Okazaki, Japan –Current clinical management of chronic pain is suboptimal as patients often continue to experience unpleasant pain even after the causative injury has resolved. In this study, researchers developed a treatment that modulates astrocyte activity in order to target the neuronal circuits underlying neuropathic pain.

Chronic pain’s pathophysiology involves the aberrant formation of noxious “pain-causing” circuits in somatosensory cortex (S1). Astrocytes proliferate throughout the central nervous system and are essential for environmental homeostasis. More recently, additional crucial roles in controlling synaptogenesis and synaptic maintenance have been reported. Given this growing appreciation for the importance of astrocytes in facilitating neural circuit rewiring, Junichi Nabekura and his research team at the National Institute for Physiological Sciences developed a novel approach for modulating astrocyte activity to drive circuit reorganization in neuropathic pain. They recently published their findings in Nature Communications.

“We found that pain causing neural circuits can be reorganized through artificial manipulation, and the reorganization of the pain causing circuits can cure neuropathic pain. By combining two methods currently used in clinical medicine to treat pain, we were able to demonstrate the possibility of more efficiently resolving allodynia.” says Nabekura. “We expect this achievement to lead to the development of treatments that can be applied to humans in near future.”

Established allodynia, induced by prior partial sciatic nerve ligation, was permanently alleviated by combining transient astrocyte activation in the S1 with temporary blockade of peripheral noxious afferent input by lidocaine or TTX (tetrodotoxin) application. The astrocyte activation was induced by either tDCS (transcranial direct current stimulation) or chemogenetics (DREADD system).

Furthermore, the researchers clarified that the spine turnover of L5 pyramidal neurons in S1 cortex increased during and after astrocyte activation by tDCS or chemogenetics. Thus, this therapy fostered S1 spine elimination, which is presumed to correspond with the dismantling of inappropriate neural connections that induce allodynia.

Given that tDCS and lidocaine are well-established clinical tools, this new work potentially provides a readily translatable approach for treating neuropathic pain.