|
| | | IFP | Synovial Membrane |
| Molecule | Generic Function | Localization | Findings and Function | Localization | Findings and Function |
| | | Humans | IFP adipocytes/animal models | OA pathology and pain in humans | Humans | synoviocytes/animal models | OA pathology and pain in humans |
|
Neuropeptides/
peptides hormones | | | |
|
| Substance P | (i) Act directly on vascular endothelial and smooth muscle cell
(ii) Increases capillary permeability leading to plasma extravasation and edema
(iii) Inflammation by increase of cytokines expression
(iv) Activation of immune cells
(v) Involvement in neurogenic inflammation | Sensory nerve fibers equally distributed and frequently associated with blood vessels Bohnsack et al. 2005, Witonski et al 2005 [76, 77]. | NA | (i) Nociceptive function
(ii) Neurogenic Inflammation? Bohnsack et al. 2005, Witonski et al 2005
[76, 77] | Free nerve endings and sensory fibers widely distributed
Saito et al. 2000, Bohnsack et al. 2005, Witonski et al 2005
[76, 77, 80] | (i) Stimulate release of proinflammatory cytokines (Dirmeier et al 2008) [78]
(ii) Induce synoviocyte proliferation and synovial hyperthrophy (Matayoshi et al 2005) [83]
(iii) Activate synovial mast cells (Okamura et al 2017) [84]
(iv) Vasodilatation (Walsh et al. 1992) [82] | (i) Neurogenic inflammation ? (Saito 2003, Fusco et al 2017) [85, 97] |
|
| CGRP | (i) Vasodilation
(ii) Nociceptive function | Capillaries (Aikawa et al 2017) [88] | NA | (i) Expression increases as pain increases (Aikawa et al 2017) [88]
(ii) Expression levels of were positively correlated with COX-2 (Aikawa et al 2017) [88]
(iii) Expression levels are regulated by the COX-2/mPGES-1/PGE2 pathway (Aikawa et al 2018) [91] | Synovial fibroblasts of lining layer (Aikawa et al 2017; Takano et al 2017) [88, 90] | (i) Vasodilatation (McMurdo et al 1997) [92]
(ii) Angiogenesis (Walsh et al 2015) [93]
(iii) Inflammation (Cruwys et al 1992; Mapp et al 1996)
[94, 95]
(iv) Peripheral sensitization (Walsh et al 2015 ) [93] | (i) expression levels is lower compared to IFP levels (Aikawa et al 2017) [88]
(ii) expression is regulated by the COX-2/PGE2 pathway and that elevation of synovial CGRP levels may contribute to OA pain (Takano et al 2017) [90] |
|
| NPY | (i) Food intake
(ii) Cardiovascular performance
(iii) Neuropathic pain
(iv) inflammation | NA | NA | NA | Positive sympathetic nerve fibers were located predominantly in the perivascular area of medial compartment (Saito 2003) [97] | NA | Neurogenic inflammation ? |
|
| VIP | (i) immunomodulatory
(ii) anti-inflammatory activity | NA | NA | NA | Lining synoviocytes (Juarranz et al 2008) [99] | (i) Expression is evident in cultured OA synoviocytes (Juarranz et al 2008) [99]
(ii) Peripheral sensitization in rat models (McDougall 2006, Schuelert et al 2006) [101, 102] | Peripheral sensitization? |
|
| CATHECOLAMINES | (i) Neuromodulation in central nervous system
(ii) Hormones in blood circulation
(iii) Pain perception inhibition
(iv) Anti-inflammatory | TH positive sympathetic nerve fibers (Lehner et al 2007) [68] | | Anti-inflammatory ?
Inhibition of pain perception? | Sympathetic nerve fibers and TH positive cells (fibroblasts, mast cells, granulocytes, macrophages, B cells) only in OA not in controls (Capellino et al 2010) [104] | anti-inflammatory effects in vitro and in vivo by inhibiting pro-inflammatory cytokines (Capellino et al 2010) [104] | (i) Anti-inflammatory?
(ii) Inhibition of pain perception? |
|
