Saeed AW, Ribeiro-Da-Silva A (2011) Consequences of the ablation of non-peptidergic nociceptive fibers on neurokinin-1 receptor expression by spinal lamina I neurons. Neuroscience 2011 Abstracts 804.21. Society for Neuroscience, Washington, DC.
Summary: Spinal dorsal horn lamina I projection neurons expressing the neurokinin-1 receptor (NK-1r) are important in relaying pain-related information from the periphery to the brain. These lamina I neurons have been classified, based on their morphological and physiological properties, into three types: fusiform, multipolar and pyramidal. Of these cell types, pyramidal neurons seldom express the NK-1r and are non-nociceptive. Previously, our laboratory has demonstrated in a cuff model of chronic constriction injury a de novo expression of NK-1r by pyramidal neurons, starting at the same time as the mechanical allodynia. We have also observed a similar de novo expression of NK-1r by pyramidal neurons in an animal model of arthritis. In the current study, we investigated whether the cytotoxic ablation of the non-peptidergic, isolectin B4 (IB4)-binding subpopulation of nociceptive primary afferents led to changes in NK-1r expression by the different lamina I cell types. We injected IB4 conjugated to saporin (SAP) into the left sciatic nerve of anesthetized male Sprague Dawley rats to specifically lesion IB4-positive non-peptidergic nociceptive C-fibers. Cholera toxin subunit B (CTB) was injected into the parabrachial nucleus to label lamina I projection neurons. Animals were tested for thermal and mechanical sensitivity and sacrificed from 2 weeks to 2 months post-lesion. We cut horizontal sections of spinal segments L4 and L5 and processed the tissue for IB4 binding and NK-1r and CTB immunoreactivities using immunofluorescence. IB4-SAP treated animals showed no behavioral changes compared to sham animals when tested for thermal (Hargreaves test), mechanical allodynia (von Frey test) or mechanical hyperalgesia (pin prick test) at any of the time points studied. Compared to the contralateral side and the sham group, lamina I projection neurons in the IB4-SAP treated group revealed an ipsilateral increase in the expression of NK-1r by the fusiform and multipolar neuronal populations. Nonetheless, there was no significant change in the percentage of pyramidal neurons which expressed NK-1r, which remained very low on the ipsilateral side of the IB4-SAP treated group. From these results, we infer that a loss of non-peptidergic afferents does not induce a phenotypic switch in the pyramidal neurons. However, the increase in NK-1r immunoreactivity in lamina I fusiform and multipolar neurons suggests that these cell populations may be important in maintaining the nociceptive responses in the absence of the IB4-positive non-peptidergic afferents. Finally, we suggest that a chronic pain state may be required for the de novo expression of NK-1r by pyramidal neurons.
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