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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 1. Increased CGRP expression in keratinocytes from human painful conditions.

Figure 1

A–H) Images from sections of thoracic back skin biopsies processed with polyclonal anti-human CGRPα (A–F) captured at the same camera settings, and monoclonal anti-human CGRPα (G,H) captured at a higher camera sensitivity. Keratinocyte labeling is shown between arrows. Innervation labeling is shown with arrowheads. A, B) Examples of the variations in CGRP-IL expression among keratinocytes as shown in images from the left and right side respectively in a control subject (23-year old male) that had the most intense expression encountered among six control subjects. The CGRP-IL is heterogenous among keratinocytes mostly located in the middle third of the epidermis. C, D) Examples of CGRP-IL labeling among keratinocytes in a subject (29-year-old male) that had the least difference in labeling intensity between the PHN afflicted skin (D, VAS = 6.5) and the nonpainful unafflicted mirror-image contralateral skin (C). E, F) Examples of CGRP-IL labeling in a subject (48 year-old male, VAS = 5.0) that was representative of most of the PHN afflicted skin (F) and nonpainful unafflicted mirror-image contralateral skin (E). As revealed with the polyclonal antibody, nonpainful contralateral skin consistently had less intense and more heterogenous labeling of keratinocytes, whereas PHN skin had more intense and more homogenous labeling. In both the afflicted and unafflicted skin of the PHN subjects, CGRP-IL was expressed among keratinocytes spanning most of the thickness of the epidermis. In the PHN skin, the stratum basalis was usually less intensely labeled than the more superficial strata. CGRP positive innervation (arrowheads) appears to be less in PHN skin than in contralateral skin or control skin. E–H) Comparison of polyclonal (E, F) versus monoclonal (G, H) CGRP-IL in sections from the same biopsies from the same subject. Monoclonal CGRP-IL of keratinocytes was far less intense and more heterogenous than polyclonal labeling, but was still more intense and widespread among keratinocytes in the PHN (H) versus the contralateral skin (G). Because of the higher camera sensitivity setting, innervation labeled with the monoclonal antibody appears more intense than that with the polyclonal antibody (arrowheads). I–L) Examples of polyclonal CGRP-IL among keratinocytes from the hypothenar (I, J) and lateral foot (K, L) of control subjects (I, K) and subjects with severe CRPS type 1 (J, L). CGRP-IL among keratinocytes has a very low intensity in control skin and a moderate to high intensity among CRPS skin. In the CRPS skin, there are fewer and more weakly CGRP-IL detectable axons and endings in the upper dermis and epidermis than in control skin (arrowheads). Scale bar = 65µm in A–H, 50µm in I–L. M, N) Similar to other published reports, PGP-IL of epidermal endings from healthy controls (M) and the PHN patient cohort (N) reveals decreased epidermal nerve fiber density among the active PHN and ipsilateral sites compared with a mirror-image contralateral site, in 4 of the 5 PHN subjects, whereas healthy controls showed no lateral differences.