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.
Torsney
Carole
C
Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA. ct2035@columbia.edu
MacDermott
Amy B
AB
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