Blockade of the Complement C5a Receptor Reduces Incisional Allodynia, Edema, and Cytokine Expression

Clark, J. David; Qiao, Yanli; Li, Xiangqi; Shi, Xiaoshuang; Angst, Martin S.; Yeomans, David C.

doi:10.1097/00000542-200606000-00024

Cited by 74 publications

(128 citation statements)

References 58 publications

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“…Results for both paws were averaged. The C5a receptor (C5aR) antagonist, a synthetic cyclic AcF-[OPdChaWR] peptide, was produced by the MGH peptide core and stored at Ϫ80°C (0.5 mg/ml PBS and 5% ethanol) (Clark et al, 2006). A catheter (32 gauge; Recathco) was implanted into the intrathecal space of the vertebral column with its tip at the lumbar (L3-L5) level through a cisternal incision.…”

Section: Methodsmentioning

confidence: 99%

Complement Induction in Spinal Cord Microglia Results in Anaphylatoxin C5a-Mediated Pain Hypersensitivity

Griffin¹,

Costigan²,

Brenner³

et al. 2007

J. Neurosci.

218

225

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Microarray expression profiles reveal substantial changes in gene expression in the ipsilateral dorsal horn of the spinal cord in response to three peripheral nerve injury models of neuropathic pain. However, only 54 of the 612 regulated genes are commonly expressed across all the neuropathic pain models. Many of the commonly regulated transcripts are immune related and include the complement components C1q, C3, and C4, which we find are expressed only by microglia. C1q and C4 are, moreover, the most strongly regulated of all 612 regulated genes. In addition, we find that the terminal complement component C5 and the C5a receptor (C5aR) are upregulated in spinal microglia after peripheral nerve injury. Mice null for C5 had reduced neuropathic pain sensitivity, excluding C3a as a pain effector. C6-deficient rats, which cannot form the membrane attack complex, have a normal neuropathic pain phenotype. However, C5a applied intrathecally produces a dose-dependent, slow-onset cold pain in naive animals. Furthermore, a C5aR peptide antagonist reduces cold allodynia in neuropathic pain models. We conclude that induction of the complement cascade in spinal cord microglia after peripheral nerve injury contributes to neuropathic pain through the release and action of the C5a anaphylatoxin peptide.

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Section: Methodsmentioning

confidence: 99%

Complement Induction in Spinal Cord Microglia Results in Anaphylatoxin C5a-Mediated Pain Hypersensitivity

Griffin¹,

Costigan²,

Brenner³

et al. 2007

J. Neurosci.

218

225

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“…A cut in the skin and subcutaneous tissues during the surgical incision causes damage to the tissues; this stimulates peripheral nociceptors resulting in pain sensation [7]. In addition, inflammation of the wound can arouse the nociceptors resulting in pain sensation [7,8]. Different short-or medium-acting sedatives, narcotics, and local anesthesia have been employed during the operation as an aide-de-camp to anesthesia or to alleviate postoperative pain.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Controlled Trial on Efficacy and Safety of Trocar-Site Infiltration with Lidocaine for Postoperative Pain Relief after Diagnostic Laparoscopy

Joe-Ikechebelu

Eleje

Ugwu

et al. 2018

Gynecol Obstet Invest

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Background/Aims: To compare the efficacy and safety of trocar-site infiltration with lidocaine and no intervention for postoperative pain relief after diagnostic laparoscopy. Methods: A randomized clinical trial of women with infertility scheduled for diagnostic laparoscopy without additional procedures in Life Institute for Endoscopy at Life Specialist Hospital, Nnewi, Nigeria. One hundred and ninety nine women were assigned at random to either trocar-site infiltration with lidocaine (n = 100) or no intervention (n = 99). Pain was assessed using visual analogue scale (VAS) scores at 2 and 4 h post surgery. The primary endpoints were postoperative pain control and time to first request of analgesia, while the secondary endpoints were total analgesic consumption, shoulder pain, and side effects. Evaluations between the groups were done according to the principle of intention-to-treat. Results: Baseline characteristics were similar. A nonsignificant reduction was observed in the VAS in the intervention group at base line, 2 and 4 hours into the postoperative period in comparison with no intervention (p > 0.05), and the time to first analgesic requirement was not significantly prolonged (p > 0.05). The mean total consumption of rescue analgesia was not significantly reduced (p > 0.05). Conclusions: Postoperative injection of lidocaine in laparoscopy port sites did not significantly improve pain scores after diagnostic laparoscopy. Clinical trial registration: PACTR201611001263105

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“…There are studies that demonstrated the involvement of proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) 9 , and the nerve growth factor (NGF) 10 in the induction and maintenance of pain in injured peripheral tissue (as found in surgeries). These proinflammatory substances play important roles in mediating exaggerated pain conditions 11 .…”

mentioning

confidence: 99%

Ameliorative Potential of Standardized Extract of Condalia buxifolia Reissek in Attenuating the Postoperative Pain: Evidence for the Inhibition of AMPA and Kainate in the Spinal Cord

Simões¹,

Coelho²,

Zambenedetti³

et al. 2017

PBJ

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Acute pain post-surgery is one of the major problems of public health, and its treatment is still a challenge. In this study, it was investigated the analgesic effect of a standardized methanolic extract of Condalia buxifolia (MECb) (30 and 100 mg/kg, i.g.) in a plantar incision surgery (PIS) model in mice, and the possible mechanism that underlying its effect. The effect of MECb was evaluated on the hyperalgesia (mechanical, cold and heat stimuli), and in this same model, it was analyzed the effect of MECb (100 mg/kg, i.g.) on the concentration of cytokines (TNF-α, IL-1β, IL-10) and nerve growth factor (NGF) in the paw and spinal cord.Further we investigated the effects of MECb (100 mg/kg, i.g.) on the nocifensive behaviour (spontaneous pain and hyperalgesia) induced by AMPA and kainate. Moreover, the safety profile of prolonged treatment with MECb (100 and 300 mg/kg, i.g.) and involvement of C fibers sensitive to capsaicin in its effect (100 mg/kg, i.g.) was evaluated. MECb showed a marked reduction on mechanical and heat hyperalgesia, and reduced the concentrations of TNF-α, IL-1β, and NGF. The treatment with MECb prevented the nocifensive behaviour and central sensitization caused by AMPA and kainate. Moreover, the analgesic effect of MECb was not affected by the ablation of the central afferent C fibers, and it showed reduced toxicity, indicating good safety and efficacy. The current data showed, for the first time, the analgesic and anti-inflammatory effect of MECb in an animal model of postoperative pain.The results support and suggest the use of MECb as an alternative treatment and a possible source of analgesics substances to postoperative pain.

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Blockade of the Complement C5a Receptor Reduces Incisional Allodynia, Edema, and Cytokine Expression

Cited by 74 publications

References 58 publications

Complement Induction in Spinal Cord Microglia Results in Anaphylatoxin C5a-Mediated Pain Hypersensitivity

Complement Induction in Spinal Cord Microglia Results in Anaphylatoxin C5a-Mediated Pain Hypersensitivity

A Randomized Controlled Trial on Efficacy and Safety of Trocar-Site Infiltration with Lidocaine for Postoperative Pain Relief after Diagnostic Laparoscopy

Ameliorative Potential of Standardized Extract of Condalia buxifolia Reissek in Attenuating the Postoperative Pain: Evidence for the Inhibition of AMPA and Kainate in the Spinal Cord

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