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Complex regional pain syndrome

intradermal injection of phenylephrine evokes pain and hyperalgesia in a subgroup of patients with upregulated α1-adrenoceptors on dermal nerves

Drummond, Peter D.a,*; Morellini, Nataliea,b; Finch, Philip M.a; Birklein, Franka,c; Knudsen, Lone F.d,e,f

doi: 10.1097/j.pain.0000000000001335
Research Paper

The aim of this study was to determine whether upregulated cutaneous expression of 1-adrenoceptors">α1-adrenoceptors1-AR) is a source of pain in patients with complex regional pain syndrome (CRPS). Immunohistochemistry was used to identify α1-AR on nerve fibres and other targets in the affected and contralateral skin of 90 patients, and in skin samples from 38 pain-free controls. The distribution of α1-AR was compared between patients and controls, and among subgroups of patients defined by CRPS duration, limb temperature asymmetry, and diagnostic subtype (CRPS I vs CRPS II). In addition, α1-AR expression was investigated in relation to pain and pinprick hyperalgesia evoked by intradermal injection of the α1-AR agonist phenylephrine. Expression of α1-AR on nerve bundles in the CRPS-affected limb was greater in patients who reported prolonged pain and pinprick hyperalgesia around the phenylephrine injection site than in patients with transient pain after the injection. In addition, α1-AR expression in nerve bundles was greater in patients with CRPS II than CRPS I, and was greater in acute than more long-standing CRPS. Although less clearly associated with the nociceptive effects of phenylephrine, α1-AR expression was greater on dermal nerve fibres in the painful than contralateral limb. Together, these findings are consistent with nociceptive involvement of cutaneous α1-AR in CRPS. This involvement may be greater in acute than chronic CRPS, and in CRPS II than CRPS I.

Intradermal injection of phenylephrine evoked prolonged pain and pinprick hyperalgesia in CRPS patients with histochemical signs of α1-adrenoceptor upregulation in dermal nerve bundles.

aPain Research Unit, School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia

bSchool of Medicine, University of Notre Dame, Fremantle, Western Australia, Australia

cDepartment of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

dDanish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark

eSpinal Cord Injury Centre of Western Denmark, Viborg Regional Hospital, Viborg, Denmark

fDanish National Rehabilitation Center for Neuromuscular Diseases, Aarhus, Denmark

Corresponding author. Address: School of Psychology and Exercise Science, Murdoch University, Perth 6150, Western Australia, Australia. Tel.: +61 893602415. E-mail address: P.Drummond@murdoch.edu.au (P.D. Drummond).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received March 10, 2018

Received in revised form June 18, 2018

Accepted June 28, 2018

© 2018 International Association for the Study of Pain
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