Light touch induces ERK activation

J Neurochem. 2010 Oct;115(2):505-14. doi: 10.1111/j.1471-4159.2010.06946.x. Epub 2010 Aug 31. Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia. Gao YJ, Ji RR. Source Department of Anesthesiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. yjing@zeus.bwh.harvard.edu Abstract Activation of extracellular signal-regulated kinase (ERK) in spinal cord neurons could serve as a marker for sensitization of dorsal horn neurons in persistent pain. ERK is normally activated by high-threshold noxious stimuli. We investigated how low-threshold mechanical stimuli could activate ERK after complete Freund's adjuvant (CFA)-induced inflammation. Unilateral injection of CFA induced ipsilateral heat hyperalgesia and bilateral mechanical allodynia. CFA-induced ERK activation in ipsilateral dorsal horn neurons declined after 2 days. Interestingly, low-threshold mechanical stimulation given by light touch either on the inflamed paw or the contralateral non-inflamed paw dramatically increased ERK phosphorylation in the dorsal horn ipsilateral to touch stimulation. Notably, light touch induced ERK phosphorylation mainly in superficial neurons in laminae I-IIo. Intrathecal administration of the astroglial toxin L-α-aminoadipate on post-CFA day 2 reversed CFA-induced bilateral mechanical allodynia but not heat hyperalgesia. Furthermore, L-α-aminoadipate, the glial inhibitor fluorocitrate, and a peptide inhibitor of c-Jun N-terminal Kinase all reduced light touch-evoked ERK activation ipsilateral to touch. Collectively, these data suggest that (i) ERK can be activated in superficial dorsal horn neurons by low-threshold mechanical stimulation under pathological condition and (ii) ERK activation by light touch is associated with mechanical allodynia and requires an astrocyte network. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.