Selective C-fiber deafferentation of the spinal dorsal horn prevents lesion-induced transganglionic transport of choleragenoid to the substantia gelatinosa in the rat

Abstract Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

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C-fiber Responses of Wide Dynamic Range Neurons in the Spinal Dorsal Horn of the Cat

PAIN RESEARCH ◽

10.11154/pain.8.61 ◽

1993 ◽

Vol 8 (2) ◽

pp. 61-69 ◽

Cited By ~ 1

Author(s):

Fumihiko Hanai ◽

Toshikatsu Yokota

Keyword(s):

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Dynamic Range ◽

Wide Dynamic Range ◽

Spinal Dorsal ◽

C Fiber ◽

Wide Dynamic Range Neurons

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In Vivo Patch-Clamp Analysis of IPSCs Evoked in Rat Substantia Gelatinosa Neurons by Cutaneous Mechanical Stimulation

Journal of Neurophysiology ◽

10.1152/jn.2000.84.4.2171 ◽

2000 ◽

Vol 84 (4) ◽

pp. 2171-2174 ◽

Cited By ~ 85

Author(s):

Keita Narikawa ◽

Hidemasa Furue ◽

Eiichi Kumamoto ◽

Megumu Yoshimura

Keyword(s):

Patch Clamp ◽

Receptor Antagonist ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Substantia Gelatinosa ◽

Mechanical Stimuli ◽

Patch Clamp Technique ◽

Spinal Dorsal ◽

Postsynaptic Currents

To know a functional role of inhibitory synaptic responses in transmitting noxious and innoxious information from the periphery to the rat spinal dorsal horn, we examined inhibitory postsynaptic currents (IPSCs) elicited in substantia gelatinosa (SG) neurons by mechanical stimuli applied to the skin using the newly developed in vivo patch-clamp technique. In the majority (80%) of SG neurons examined, a brush stimulus applied to the ipsilateral hind limb produced a barrage of IPSCs that persisted during the stimulus, while a pinch stimulus evoked IPSCs only at its beginning and end. The pinch-evoked IPSCs may have been caused by a touch that occurs at the on/off time of the pinch. The evoked IPSCs were blocked by either a glycine-receptor antagonist, strychnine (4 μM), or a GABAA-receptor antagonist, bicuculline (20 μM). All SG neurons examined received inhibitory inputs from a wide area throughout the thigh and lower leg. When IPSCs were examined together with excitatory postsynaptic currents (EPSCs) in the same neurons, a brush evoked a persistent activity of both IPSCs and EPSCs during the stimulus while a pinch evoked such an activity of EPSCs but not IPSCs. It is suggested that innoxious mechanical stimuli activate a GABAergic or glycinergic circuitry in the spinal dorsal horn. This inhibitory transmission may play an important role in the modulation of noxious information in the SG.

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