Table 3.
Sex-independent cellular and molecular neuroimmune mechanisms driving pain hypersensitivity
| Model | Cell Type(s) | Mediator | Rodent | REF |
|---|---|---|---|---|
| Nerve injury (SNT) | Spinal glia | Spinal soluble TNF and IL-1b | Holzman rats | 211 |
| Not specified | IL-6; allodynia F = M; autotomy behavior F > M | C57BL/6 × 129/BV/SV mice | 245 | |
| Microglia | CXCR1+ microglia | C57BL/6 mice | 179 | |
| C40+ spinal microglia interaction with infiltrating CD4+ T-cells | Balb/c mice | 34,36 | ||
| T-cells | Cd4+ T-cell infiltration into ipsilateral spinal cord | Balb/c mice | 35 | |
| Nerve injury (CCI) | Microglia | Phospho-P38 MAPK in males | CD-1 mice; Sprague Dawley rats | 216 |
| CXCR1+ microglia | CD-1 mice; Sprague Dawley rats | 216, 248 | ||
| P2X4+ microglia | Sprague Dawley rats | 142 | ||
| TNFR1-induced NMDA1 activation in spinal cord, cortex | C57BL/6 mice | 56 | ||
| Macrophages | CD68, Cd11b+ macrophages; tactile allodynia F = M | C57BL/6 mice | 44 | |
| T-cells | TNFR2 essential for recovery | C57BL/6 mice | 76 | |
| Nerve injury (SNI) | Microglia | P2X7 | Sprague Dawley rats | 54 |
| Nerve injury (pSNL) | Not specified | P2X7 | C57BL/6 mice | 41 |
| Postoperative pain | DRG nneurons | PRLR in females | C57BL/6.129 mice; Sprague Dawley rats | 178 |
| Microglia | Phospho-P38 MAPK in males | Sprague Dawley rats | 165 | |
| Macrophage, Mast cells, Neutrophils, | NLRP3-dependent IL-1b release in DRG and peri-incisional skin in males; NLRP3-independent in females | C57BL/6j, C57BL/6N/129 mice | 50 | |
| Mast cells | Mrgprb2 | C57BL/6 mice | 85 | |
| Complex regional pain syndrome (CRPS) | Microglia (males), T-cells (females), B-cells (both) | Spinal IL-6, NK1 in males; delayed adaptive immune response in females | C57BL/6J mice | 89 |
| IPLT Zymosan | Not specified | TLR2 | CD-1 mice | 205 |
| IPLT CFA | Neurons | High-affinity tonic GABAA current in PAG | Sprague Dawley rats | 222 |
| Not specified | Spinal TLR4, serum, TNFa, IL-1b, and IL-6 in males | CD-1 mice; Sprague Dawley rats | 26,205 | |
| IPLT Formalin | Glia, Neurons (males); T-cells (females) | DRD1, DRD3 in females; DRD4 in males; BDNF, TLR4 in both sexes | CD-1, C57BL/6J, C57BL/6/129.P2 mice | 130,149,193 202,243 |
| Muscle Hyperalgesia | Macrophages | P2X4+ resident macrophages, TLR4, IL-6 | C57BL/6 mice | 83 |
| IPLT TNFa | Not specified | Peripheral TRPA1, central TRPV1; mixed males and females | C57BL/6J.129.SvJ, CD-1 mice | 66 |
| IPLT Angiogensin II | Macrophages, Neurons | AT2R in skin macrophages transactivates TRPA1 in neurons | C57BL/6J, FVB/NJ mice | 199 |
| Hyperalgesic Priming | Neurons | Spinal DRD5 in males; DRG PRLR in females | C57BL/6J.129, C57BL/6J mice | 149,178 |
| IT BDNF | Microglia | Spinal KCC2 downregulation | CD-1 mice | 143 |
| IT NRG-1 | Astrocytes, Neurons | Spinal ErbB | Sprague Dawley rats | 118 |
| IT LPS | Not specified | Spinal TLR4 | SWR/J mice | 106 |
| ICV LPS | Not specified | TLR4 | CD-1 mice | 205 |
| Intra-PAG LPS | Microglia | TLR4 | Sprague Dawley rats | 61 |
| IPLT LPS | Not specified | TLR4 | CD-1 mice | 205 |
| Systemic Bacteremia (IP LPS, neonatal) | Microglia, Not specified | Spinal TLR4, Spinal COX2; Downregulation of Oprm1 in PAG, PFC | Sprague Dawley rats | 21,95,246 |
| Migraine (Intracisternal IL-6) | Not specified | BDNF | Sprague Dawley rats | 30 |
| IA Carrageenan | Immune cells (in joint) | P2X2 and P2X3 in both sexes; P2X7 in females | Wistar rats | 217,218 |
| IA CFA | Not specified | TRPA1, TRPV1, TNFa | CD-1, C57BL/6J mice | 66 |
| Collagen antibody-induced arthritis (CAIA) | Glia, Neurons (spinal); Macrophages | Macrophage HMGB1/TLR4 in males; Nociceptor TLR4 in females | Balb/c mice | 2,67,195 |