Research article summary (published 24 May 2009):

The role of enhanced cutaneous IL-1beta signaling in a rat tibia fracture model of complex regional pain syndrome.

Full Abstract

Tibia fracture in rats initiates a syndrome resembling the complex regional pain syndrome type I. Accumulating evidence indicates that IL-1beta is involved in the modulation of nociceptive information and it acts as an intermediate inflammatory mediator via up-regulation of NGF. We hypothesized that IL-1beta signaling might mediate the development of the CRPS-like changes after tibial fracture, either directly or by stimulating NGF expression. Rats underwent distal tibia fracture and casting for 4 weeks and were chronically treated with an IL-1 receptor antagonist (IL-1ra). Nociceptive testing and assessment of edema and hindpaw warmth were performed at baseline and after cast removal. Bone microarchitecture was evaluated by micro-computed tomography. Confocal immunofluorescence and in situ hybridization techniques were used to evaluate changes in the cutaneous expression of IL-1beta at 4 weeks post-fracture. The nociceptive and vascular effects of intraplantar IL-1beta injections were evaluated in intact rats at different time points after injection. We found that: (1) IL-1ra reduced fracture-induced nociceptive sensitization, but did not decrease hindpaw edema or warmth, (2) fracture chronically up-regulated IL-1beta mRNA and protein expression in hindpaw skin keratinocytes, (3) IL-1beta intraplantar injection induced mechanical allodynia in a dose-dependent manner and stimulated keratinocyte NGF expression in the hindpaw skin, and (4) intraplantar injection of NGF-induced nociceptive sensitization. Collectively, these results indicate that cutaneous IL-1beta signaling can contribute to chronic regional nociceptive sensitization after fracture, possibly by stimulating NGF over-expression in keratinocytes. Our data also highlight the importance of the keratinocyte as the primary source of post-traumatic IL-1beta over-expression.

Author information

Author/s: Li, Wen-Wu (WW); Sabsovich, Ilya (I); Guo, Tian-Zhi (TZ); Zhao, Rong (R); Kingery, Wade S (WS); Clark, J David (JD);

Affiliation: Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.

Grants: GM079126 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Pain (Pain), published in Netherlands. (Language: eng)

Reference: 2009-Aug; vol 144 (issue 3) : pp 303-13

Dates: Created 2009/07/07; Completed 2009/09/30;

PMID: 19473768, status: MEDLINE (last retrieved date: 9/30/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Disease Models, Animal Edema - etiology; physiopathology Foot - innervation; physiopathology Gene Expression Regulation - drug effects; physiology Hyperemia - etiology; physiopathology Inflammation - etiology; metabolism; physiopathology Interleukin 1 Receptor Antagonist Protein - pharmacology Interleukin-1beta - antagonists & inhibitors; genetics; metabolism Keratinocytes - metabolism; secretion Male

Nerve Growth Factor - metabolism; pharmacology; secretion Nociceptors - metabolism Pain Measurement RNA, Messenger - metabolism Rats Rats, Sprague-Dawley Reflex Sympathetic Dystrophy Sensory Receptor Cells - metabolism; secretion Skin - innervation; physiopathology Tibial Fractures - complications Up-Regulation - physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Interleukin 1 Receptor Antagonist Protein (0) ; Interleukin-1beta (0) ; RNA, Messenger (0) ; Nerve Growth Factor (9061-61-4)

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