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Increased local concentration of complement C5a contributes to incisional pain in mice.
J Neuroinflammation. 2011 Jul 07; 8:80.JN

Abstract

BACKGROUND

In our previous study, we demonstrated that local injection of complement C5a and C3a produce mechanical and heat hyperalgesia, and that C5a and C3a activate and sensitize cutaneous nociceptors in normal skin, suggesting a contribution of complement fragments to acute pain. Other studies also have shown that the complement system can be activated by surgical incision, and the systemic blockade of C5a receptor (C5aR) reduces incision-induced pain and inflammation. In this study, we further examined the possible contribution of wound area C5a to incisional pain.

METHODS

Using of a hind paw incisional model, the effects of a selective C5aR antagonist, PMX53, on nociceptive behaviors were measured after incision in vivo. mRNA levels of C5 and C5aR in skin, dorsal root ganglia (DRG) and spinal cord, and C5a protein levels in the skin were quantified after incision. The responses of nociceptors to C5a were also evaluated using the in vitro skin-nerve preparation.

RESULTS

Local administration of PMX53 suppressed heat hyperalgesia and mechanical allodynia induced by C5a injection or after hind paw incision in vivo. mRNA levels of C5 and C5aR in the skin, but not DRG and spinal cord, were dramatically increased after incision. C5a protein in the skin was also increased after incision. In vitro C5a did not increase the prevalence of fibers with ongoing activity in afferents from incised versus control, unincised skin. C5a sensitized C-fiber afferent responses to heat; however, this was less evident in afferents adjacent to the incision. PMX53 blocked sensitization of C-fiber afferents to heat by C5a but did not by itself influence ongoing activity or heat sensitivity in afferents innervating control or incised skin. The magnitude of mechanical responses was also not affected by C5a in any nociceptive fibers innervating incised or unincised skin.

CONCLUSIONS

This study demonstrates that high locally generated C5a levels are present in wounds for at least 72 hours after incision. In skin, C5a contributes to hypersensitivity after incision, but increased responsiveness of cutaneous nociceptors to C5a was not evident in incised skin. Thus, high local concentrations of C5a produced in wounds likely contribute to postoperative pain.

Authors+Show Affiliations

Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21736743

Citation

Jang, Jun H., et al. "Increased Local Concentration of Complement C5a Contributes to Incisional Pain in Mice." Journal of Neuroinflammation, vol. 8, 2011, p. 80.
Jang JH, Liang D, Kido K, et al. Increased local concentration of complement C5a contributes to incisional pain in mice. J Neuroinflammation. 2011;8:80.
Jang, J. H., Liang, D., Kido, K., Sun, Y., Clark, D. J., & Brennan, T. J. (2011). Increased local concentration of complement C5a contributes to incisional pain in mice. Journal of Neuroinflammation, 8, 80. https://doi.org/10.1186/1742-2094-8-80
Jang JH, et al. Increased Local Concentration of Complement C5a Contributes to Incisional Pain in Mice. J Neuroinflammation. 2011 Jul 7;8:80. PubMed PMID: 21736743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased local concentration of complement C5a contributes to incisional pain in mice. AU - Jang,Jun H, AU - Liang,Deyong, AU - Kido,Kanta, AU - Sun,Yuan, AU - Clark,David J, AU - Brennan,Timothy J, Y1 - 2011/07/07/ PY - 2011/05/02/received PY - 2011/07/07/accepted PY - 2011/7/9/entrez PY - 2011/7/9/pubmed PY - 2012/2/24/medline SP - 80 EP - 80 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 8 N2 - BACKGROUND: In our previous study, we demonstrated that local injection of complement C5a and C3a produce mechanical and heat hyperalgesia, and that C5a and C3a activate and sensitize cutaneous nociceptors in normal skin, suggesting a contribution of complement fragments to acute pain. Other studies also have shown that the complement system can be activated by surgical incision, and the systemic blockade of C5a receptor (C5aR) reduces incision-induced pain and inflammation. In this study, we further examined the possible contribution of wound area C5a to incisional pain. METHODS: Using of a hind paw incisional model, the effects of a selective C5aR antagonist, PMX53, on nociceptive behaviors were measured after incision in vivo. mRNA levels of C5 and C5aR in skin, dorsal root ganglia (DRG) and spinal cord, and C5a protein levels in the skin were quantified after incision. The responses of nociceptors to C5a were also evaluated using the in vitro skin-nerve preparation. RESULTS: Local administration of PMX53 suppressed heat hyperalgesia and mechanical allodynia induced by C5a injection or after hind paw incision in vivo. mRNA levels of C5 and C5aR in the skin, but not DRG and spinal cord, were dramatically increased after incision. C5a protein in the skin was also increased after incision. In vitro C5a did not increase the prevalence of fibers with ongoing activity in afferents from incised versus control, unincised skin. C5a sensitized C-fiber afferent responses to heat; however, this was less evident in afferents adjacent to the incision. PMX53 blocked sensitization of C-fiber afferents to heat by C5a but did not by itself influence ongoing activity or heat sensitivity in afferents innervating control or incised skin. The magnitude of mechanical responses was also not affected by C5a in any nociceptive fibers innervating incised or unincised skin. CONCLUSIONS: This study demonstrates that high locally generated C5a levels are present in wounds for at least 72 hours after incision. In skin, C5a contributes to hypersensitivity after incision, but increased responsiveness of cutaneous nociceptors to C5a was not evident in incised skin. Thus, high local concentrations of C5a produced in wounds likely contribute to postoperative pain. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/21736743/Increased_local_concentration_of_complement_C5a_contributes_to_incisional_pain_in_mice_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-8-80 DB - PRIME DP - Unbound Medicine ER -