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. Author manuscript; available in PMC: 2012 Sep 1.
Published in final edited form as: Pain. 2011 Jun 17;152(9):2036–2051. doi: 10.1016/j.pain.2011.04.033

Figure 3. Hindpaw inflammation increases CGRP expression in epidermal keratinocytes.

Figure 3

A–D) CFA hindpaw injection time course, depicting in each vertical panel, representative double label (CGRP/PGP) results from glabrous pad crown (A–D), dermal vasculature (‘), and dermal nerve (‘’), with each separate channel split below or to the left of the double label image. A) Control uninjected rats depicting CGRP-IL of a subset of innervation (PGP-IL, green) among the epidermal endings and subepidermal plexus (yellow arrows). The separate channels are split below the double labeled images. Epidermal keratinocyte CGRP-IL (red chevrons) appeared heterogeneous and weak among the volar pad crown. A’) Neural innervation to dermal vasculature contained a mix of CGRP-IL-positive and CGRP-IL-negative axons among the tunica media and advential layers. A”) Dermal nerves contained a rich contingent of CGRP-IL axons. B) By 2 hrs after CFA injection, increased CGRP expression is apparent among epidermal keratinocytes, with little change among the innervation of the epidermis, subepidermal plexus, dermal vasculature (B’), or in the composition of dermal nerves (B”). C) By 3 days after CFA injection, epidermal CGRP expression is increased among suprabasal keratinocytes, while neural innervation appears depleted (i.e., lack of CGRP or PGP axon staining) from the epidermis and subepidermal plexus. C’) Interestingly, among the dermal vasculature, a dramatic loss of CGRP immunopositive medial and adventitial innervation is observed, although PGP immunopositive axons are still present. Dermal nerves appear distraught with ragged PGP labeling and limited CGRP axons present (C”). D) By 14 days following CFA, epidermal CGRP expression remains elevated among the most suprabasal keratinocytes, and immunopositive axons are absent from the epidermis or subepidermal plexus. D’) Dermal vasculature appeared without CGRP immunopositive innervation among the medial and adventitial layers, although PGP immunopositive axons were still present, and dermal nerves remained distraught in appearance with limited CGRP axons (D”). Magnification bar (A) =50µm for A–D, and =25µm for (‘) and (‘’). Anti-CGRP (guinea pig polyclonal, 1:800; Peninsula Labs, San Carlos, CA) and anti-PGP (rabbit polyclonal, 1:1000; UltraClone, Wellow, UK) were used.