부산대학교 도서관

Chemokines are expressed by immune cells and cause monocyte extravasation at a site of tissue injury. They are divided into 4 families; CC, CXC, C and CX3C. There is evidence for involvement of several chemokines in pain mechanisms, notably CX3CL1, CCL2 and CX3C (Old & Malcangio, 2012). Their role is not fully understood but they are linked to mechanisms of neuron-glia communication and altered excitability of pain pathways following neuropathic or inflammatory injury (Ren & Dubner, 2010). Lymphotactin (XCL1), the only member of group C, is chemotactic for lymphocytes and mediates its effects via its cognate receptor XCR1. The role of lymphotactin and XCR1 in nociception and pain is unknown. We have used immunohistochemistry to characterize expression of XCR1 within nociceptive areas of the adult rat spinal and trigeminal dorsal horn (DH). All procedures were carried out in accordance with UK Home Office legislation. Under irreversible anaesthesia (pentobarbital, 50 mg/kg i.p.) and after transcardiac perfusion-fixation, the spinal trigeminal nucleus caudalis (Vc) of the caudal brainstem and spinal cords were removed from rats (Wistar, 28 days). Brainstem (caudal to obex) and spinal cord (cervical and lumbar) transverse sections (30 µm) were cut and processed for immunofluorescence visualization of XCR1 either alone or in co-labelling studies with the vesicular glutamate transporters VGLUT 1 or VGLUT2 which mark glutamatergic synaptic terminals. Confocal imaging of spinal cord sections revealed intense labelling for XCR1 within nociceptive DH laminae I and II. Similarly, intense XCR1 labelling was localized to the most superficial layers of Vc and was also within the spinal trigeminal tract (STt). The diffuse pattern of labelling was indicative of an axonal or fibre localization rather than in cell bodies. In double-labelling studies with either VGLUT1 or VGLUT2, labelling for XCR1 in either spinal or Vc DH overlapped extensively with VGLUT2 in superficial layers whereas VGLUT1 staining was distributed to deeper regions with little evidence of overlap. This pattern of staining infers that XCR1 may be expressed on either the terminals of excitatory DH interneurons or small diameter nociceptive primary afferents, putatively A-delta or C-fibre subtypes in these two CNS regions (Todd et al., 2003). Taken together, these observations reveal, for the first time, the expression of XCR1 within structures that are key areas in the transmission and subsequent modulation of nociceptive signals that give rise to both acute and chronic pain. These data may have important implications for the role of novel chemokines in the pathogenesis of chronic pain, including trigeminal oro-facial pain. [ABSTRACT FROM AUTHOR]