Table 1: Summary of cited studies on the role of complement in experimental and disease-related pain.

Pain Model Organism Experimental Endpoints Measured/span> Anti Complement Agent Result References
Opioid Pain Relief Mice Anti-analgesic effect C3a C3a reduces the analgesic effect on mice treated with opioid pain medication [27, 28]
Sciatic Nerve Ligation Rat Mechanical Allodynia Cold Allodynia C5aR antagonist AcF-[OPdChaWR] Less mechanical and cold allodynia in mice treated with C5aR antagonist [38]
C6 (-/-) rats Mechanical Allodynia Cold Allodynia NA Normal neuropathic pain phenotype, MAC not involved
Sciatic Nerve Ligation Rat Mechanical hyperalgesia CVF Complement depletion reduces pain behavior [26]
Sciatic Nerve Ligation Rat Thermal Hyperalgesia Mechanical Allodynia Soluble Complement receptor (sCR1) C3 deposition seen after SCL and IgG injection, accompanied by macrophage recruitment. sCR1 Injections resulted in less TH and MA. [25]
Spinal inflammatory Neuropathy Caused by Zymosan, GP120, and chronic constriction injury Rat Mechanical Allodynia sCR1 sCR1 injection reduces mechanical allodynia. [23]
Sciatic Nerve Crush Rat Macrophage infiltration and activation Conmplement inhibitor: Cobra Venom Factor (CVF) Less macrophage infiltration in CVF-treated animals. [20]
Sciatic Nerve Chronic constriction injury Mouse Hyperalgesia CVF Mice given daily injections of CVF had less hyperalgesia. 1 CVF injection 4 days after surgery greatly reduced hyperalgesia. [30]
Paw Incision Mouse Incisional Allodynia and Edema AcF-[OPdChaWR] Daily injection of AcF-[OPdChaWR] reduces incisional edema and allodynia. [35]
Paw injection Mouse Heat and Mechanical Hyperalgesia NA C5a injection elicits both heat and mechanical hyperalgesia, while C3a injection elicits only mechanical hyperalgesia [45]
Paw injection Mouse Heat Hyperalgesia and Mechanical Allodynia PMX53 (C5aR antagonist) Injection of PMX53 reduces both heat hyperalgesia and mechanical allodynia caused by injection of C5a [46]
Paw Injection Rat Edema Vinblastine C5a -induced hypernociception reduced when neutraphils reduced by vinblastin treatment. [43]
Hypernociception caused by injection of zymosan, carrageenan, LPS, and antigen. PMX53 PMX53 injection reduced hypernociception.
Rheumatoid Arthritis Human C5a NA C5a levels increased in rheumatoid joint fluids. Neutraphils increased in synovial fluid. [53]
Sickle Cell Anemia Human Pain, C3a, C3, Bb, C4d, NA Measured complement levels in patients suffering severe painful episodes vs. base levels. Complement activation was higher during painful episodes. [24]
C5a Injection into hindpaw Rat Nociception Hydroxyurea C5a is a chemotactic peptide, and injection into hindpaw of rats induces hyperalgesia. In addition, PML supernatant also causes hyperalgesia. When PMLs reduced by hydroxyurea treatment, hyperalgesia reduced. [33]
anti-ganglioside GD2 antibody-induced pain Rat Hindpaw allodynia Non complement-fixing antibody GD2 antibody Mice treated with mutant antibody with reduced CDC activity had faster resolving allodynia than those injected with "normal" antibody. C6 knockout mice had reduced allodynia, while C5aR antagonist eliminated allodynia. [47]
C5a receptor knockout Mouse Pain, edema C5aR knockout vs. normal. In C5aR-/- mice, thermal nociceptive pain reduced for 4 days post-incision, while mechanical sensitivity reduced only after 48 hrs. C5aR-/- showed little edema, while wt mice showed normal edema. [37]
Hematuria/Groin Pain Human C3b NA Patients with loin pain and Haematuria had C3b deposition on arteriolar walls. [16]
Spinal Cord Injury Rat Macrophages Vaccinia Virus Complement Control Protein (VCP) VCP injection following spinal cord injury inhibits macrophage infiltration and improves hind limb function. [17]
CFA and C5a injection Mice Threshold of pain PMX53, knockout mice Showed that pain is mediated by activation of TRPV1 ion channels. NGF is one activator of TRPV1. [49]
Inflammatory and neuropathic pain Mice Hyperalgesia DF2593A Showed injection of mice with DF2593A reduces inflammatory and neuropathic pain [52]