Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord.
Blockade of local spinal cord inhibition mimics the behavioral hypersensitivity that manifests in chronic pain states. This suggests that there is a pathway capable of mediating allodynia/hyperalgesia that exists but is normally under strong inhibitory control. Lamina I and III 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 proposed pathway. To investigate, whole-cell patch-clamp recordings were made from lamina I and III NK1R+ neurons in the spinal cord slice preparation with attached dorsal root. Excitatory postsynaptic currents were recorded in response to electrical stimulation of the dorsal root. Lamina I NK1R+ neurons were shown to receive high-threshold (Adelta/C fiber) monosynaptic input, whereas lamina III NK1R+ neurons received low-threshold (Abeta fiber) monosynaptic input. In contrast, lamina I neurons lacking NK1 receptor (NK1R-) received polysynaptic A fiber input. Blockade of local GABAergic and glycinergic inhibition with bicuculline (10 microm) and strychnine (300 nm), respectively, revealed significant A fiber input to lamina I NK1R+ neurons that was predominantly Abeta fiber mediated. This novel A fiber input was polysynaptic in nature and required NMDA receptor activity to be functional. In lamina I NK1R- and lamina III NK1R+ neurons, disinhibition enhanced control-evoked responses, and this was also NMDA receptor dependent. These disinhibition-induced changes, in particular the novel polysynaptic low-threshold input onto lamina I NK1R+ neurons, may be an underlying component of the hypersensitivity present in chronic pain states.
Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA. ct2035@columbia.edu
Carole
C
Torsney
Amy B
AB
MacDermott
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D017353:Gene Deletion; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012684:Sensory Thresholds; D015398:Signal Transduction; D013116:Spinal Cord / Q000503:physiopathology*
D018040:Receptors, Neurokinin-1