TABLE 1.
Pain facilitation in animal models is prevented (p) or reversed (r) by inhibition of spinal glial activation or proinflammatory cytokine actions:
| Model | Intervention [prevention (p) vs. reversal (r) noted for each] |
|---|---|
| Bone cancer | IL-1ra (r)61 |
| Carrageenan, subcutaneous | minocycline (p), IL-1 knockout (p) |
| Chemotherapy induced neuropathy | propentofylline (SLC022) (p)62 IL-10 (r)63, IL-1ra (r)63, ibudilast (AV411) (r)64, CB2 agonist (p)65, minocycline (p)66 |
| Colon irritation | minocycline (r)67 |
| Complete Freund’s adjuvant | IL-1ra (p,r)68,69, IL-1 KO (p), fluorocitrate (p)69, CB2 agonist (r)70 |
| Dorsal root compression/inflammation | IL-1ra, sTNFR minocycline (p)71 |
| Dynorphin, intrathecal | IL-1ra (p), IL-10 (p) |
| EAE model of multiple sclerosis pain | IL-10 (r)72 |
| Facial nerve chronic constriction injury | IL-1ra (r)73 |
| Formalin, subcutaneous | fluorocitrate (p), IL-1ra (p), minocycline (p), IL-1 KO (p) |
| Fractalkine, intrathecal | minocycline (p), IL-1ra (p), anti-IL-6 (p) |
| HIV-1 gp120, intrathecal | fluorocitrate (p), IL-1ra (p), sTNFR (p), anti-IL6 (p), minocycline (p)74, IL-10 (p)75 |
| Inferior alveolar and mental nerve transection | minocycline (p) |
| Infraorbital nerve injury | propentofylline (SLC022) (r)8, fluorocitrate (r)8, minocycline (r)8, sTNFR (r)8, IL-1ra (r)8 |
| Monoarthritis | Fluorocitrate (r)6, minocycline (p)6 |
| Myositis | minocycline (p)76, anti-TNF (p)76 |
| Mustard oil, topical | fluorocitrate (p) |
| Phospholipase A2, subcutaneous | fluorocitrate (p), IL-1ra (p), sTNFR (p) |
| Postoperative incisional pain | fluorocitrate (r), IL1ra overexpressing transgenetics & IL1 receptor KO (p)77, IL-1ra (r)77, pentoxifylline (p)78, CB2 agonist (r)79 |
| Sciatic nerve injury | IL-1ra (r), IL-10 (r), IL-1 knockout (p), ibudilast (AV411) (r)58, fluorocitrate (r)80, minocycline (p)81, 82, pentoxifylline (p)81, CB2 agonist (r)70 |
| Sciatic nerve inflammation | fluorocitrate (p), minocycline (p), IL-1ra (p), sTNFR (p), anti-IL-6 (p), IL-10 (p)83 |
| Sciatic nerve tetanic stimulation | fluorocitrate (p) |
| Spinal cord injury | IL-10 (p), sTNFR (p)84, minocycline (p,r) 84,85, ibudilast (AV411) (r), propentofylline (p)86 |
| Spinal nerve root injury | methotrexate (p,r) |
| Spinal nerve transection or ligation | propentofylline (SLC022) (p,r), minocycline (p)87, ibudilast (AV411) (r)58, pentoxifylline (p)88, IL-1 KO (p), CB2 agonist (r)89, IL-1ra + sTNFR (p,r), IL-1 receptor KO (p), IL1ra overexpresssing transgenic (p) |
| Supradural “inflammatory soup” | ibudilast (AV411) (r) |
| Tempormandibular joint region inflammation | anti-IL6 (p)90 |
| Tibia fracture model of complex regional pain syndrome | pentoxifylline (p)91 |
| Zymosan, subcutaneous | fluorocitrate (r)80 |
Abbreviations: anti-IL6: neutralizing antibody against interleukin-6, anti-TNF: neutralizing antibody against tumor necrosis factor-α, CB2: cannabinoid type 2, KO: knockout mice, IL-1ra: interleukin-1 receptor antagonist, sTNFR: soluble TNF receptor, IL-10: interleukin-10.
Modified and updated from Watkins et al.7. Citations are found in this 2007 review unless otherwise indicated.