Inflammatory Pain Unmasks Heterosynaptic Facilitation in Lamina I Neurokinin 1 Receptor-Expressing Neurons in Rat Spinal Cord

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Central sensitization in inflammatory pain conditions results in behavioral mechanical hypersensitivity. Specifically, C-fiber-driven spinal hyperexcitability enables A fibers to gain access to specific spinal circuitry, via heterosynaptic facilitatory mechanisms, to mediate mechanical hypersensitivity. However, the precise circuitry engaged is not known. Lamina I neurokinin 1 (NK1) receptor expressing (NK1R(+)) dorsal horn neurons, many of which are projection neurons, are required for the development of this hypersensitivity and are therefore likely to be a component of this circuitry. To investigate, whole-cell patch-clamp recordings were made from lamina I NK1R(+) neurons in the spinal cord slice preparation with attached dorsal root, obtained from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation. EPSCs were recorded in response to electrical stimulation of the dorsal root. Control neurons predominantly received monosynaptic C-fiber input (69%) with a smaller proportion receiving monosynaptic A delta-fiber input (28%). In contrast, CFA inflammation significantly increased the incidence (by twofold) and magnitude (by 75% in a subset) of monosynaptic A delta-fiber but not monosynaptic C-fiber-evoked responses. A beta-fiber input to lamina I NK1R(+) neurons was minimal, polysynaptic in nature, and unaltered by CFA inflammation. Additional examination of control neurons revealed that a proportion received silent monosynaptic A delta-fiber input, suggesting that these may provide the substrate for the novel A delta inputs observed in CFA inflammation. This inflammation induced unmasking and strengthening of monosynaptic A delta drive to lamina I NK1R(+) neurons may contribute to the heterosynaptic facilitatory mechanisms underlying mechanical hyperalgesia in inflammatory pain.

Original languageEnglish
Pages (from-to)5158-5168
Number of pages11
JournalThe Journal of Neuroscience
Issue number13
Publication statusPublished - 30 Mar 2011


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