Studies that explore the role of innate immunity and NcP
| Study and reference | Mechanism involved | NcP condition |
|---|---|---|
| Mast cells involvement | ||
| Blanco et al. [32] | Increased mast cells correlate with pain, fatigue | FM patients |
| Salemi et al. [33] | Increased mast cells and mediators such as IL 1, IL 6, TNF-alpha, IL 17 | FM patients |
| Murphy et al. [34] | Increased mast cells and mediators such as IL 1, IL 6, TNF-alpha, IL 17 | Chronic pelvic pain patients |
| Tsilioni et al. [36] | Increase in serum substance P which increases mast cell activation | FM patients |
| Liu et al. [41] | Higher levels of mucosal leptin, linked to increased levels of mast cells through the induction of IFN and the suppression of IL 4 | IBS patients |
| Li et al. [43] | Mast cell accumulation, activation, and degranulation in proximity to peptidergic nerve fibers were mediated by substance P | CRPS patients |
| Neutrophils involvement | ||
| Caxaria et al. [46] | Neutrophils invade sensory ganglia, increasing mechanical hyperalgesia and favouring sensitization of spinal cord neurons | FM patients |
| Microglia and astrocyte activation | ||
| Atta et al. [21] | M1/M2 polarization with an augmented pro-inflammatory signature (mediated by the M1 phenotype, which secretes TNF-alpha, IL 1β, and IL 6) | FM patients |
| Ye et al. [54] | Glial activation with an increase of pro-inflammatory cytokines and overexpression of purinergic receptors | Orofacial pain patients |
| Linan-Rico et al. [55] | Enteric glia activation, linked to toll-like receptor 4 signaling | IBS patient |
| Dodds et al. [56] | Glial activation by toll-like receptors, purinergic receptors, and chemokines | Female patients with pelvic pain |
| Lao et al. [57] | Microglia activation is mediated by purinergic receptors, TNF-alpha, and IL 1β | Male patient with pelvic pain |
| Tian et al. [58] | Astrocytes activation via metalloproteinase pathway | CRPS patients |
| NK recruitment | ||
| Verma et al. [60] | NK cells recruitment and pro-inflammatory cytokines spill over | FM patients |
NcP: nociplastic pain; FM: fibromyalgia; IL: interleukin; TNF: tumor necrosis factor; IBS: irritable bowel syndrome; IFN: interferon; CRPS: complex regional pain syndrome; NK: natural killers. MI/M2 microglia phenotypes (see text for details)