Table 3

Many experiments and articles reported a modulation in the release of critical neuronal mediators in response to a large variety of interventions

Experiments (n)Articles (n)Inducer (+)/suppressor (–)Molecule linked to modulation
TNF
3419+IL-1a, IL-1b [2], LPS [2], nerve injury or inflammation (CCI, DMM, OA, microinjury at ligament flavum, monosodium urate), human disorder (FM, RA, intervertebral disc degeneration, degenerative lumbar spondylolisthesis, TMJ meniscus tears), infection (Candida albicans)+PKCgamma (KO), Wnt (inhibitor), macrophage (pharmaceutical depletion), Cyr61 (shRNA)
−TGF-b1−Foxo3 (siRNA), AMPK (inhibitor), p38 (inhibitor, siRNA), miR-92a (mimic), herbal remedy (Aralia continentalis Kitag., Betula platyphylla, Huzhang Tongfeng granule), platelet-rich plasma, vitamin E
NGF
197+IL-1b [3], TNF [2], injury (DMM [2], OA, cartilage injury, muscle injury), human disorder (OA [3])+FGF2 (KO), FGFR (inhibitor), TAK1 (inhibitor), SRC (inhibitor)
− PKCgamma (KO), Cox2 (inhibitor), PGE2 (agonist), EP (agonist)
IL-6
6432+IL-1a [3], IL-1b [12], TNF [2], HMGB1, bradykinin, PGE2, EP2, EP4, TLR7, norepinephrine,* EDPs, LPS [4], poly(I:C), infection (C. albicans [2], C. glabrata, C. tropicalis, CHIKV, HIV), zymosan, nerve inflammation (monosodium urate), human disorder (vulvodynia [3], RA [3], OA, total knee arthroplasty, ligament injury, FM, frozen shoulder)+IKKkb (OE, KO), NFkb (inhibitor) [2], Dectin1 (decoy ligand, siRNA), Wnt (inhibitor), bradykinin receptor (isRNA, inhibitor), macrophage (pharmaceutical depletion), Cox2/Cox (inhibitor) [2], IL-1R (antagonist), PKA (inhibitor)
−Dexamethasone, cannabinoid 2, phosphatidylserine, dihydroartemisinin derivative, benzylideneacetophenone derivative, gabapentin−Cannabinoid R2 (agonist), glucocolticoid receptor (siRNA), herbal remedy (piperine, Aralia continentalis Kitag., WIN-34B, Betula platyphylla, Huzhang Tongfeng granule), platelet-rich plasma, Cyr61 (shRNA)
CGRP
52+PGE2, muscle injury, human disorder (OA)
  • *Reported in headache. The numbers in square brackets indicate if a factor was used in more than one article.

  • CCI, chronic constriction injury; CHIKV, chikungunya virus; DMM, destabilisation of the medial meniscus; EDP, elastin-derived peptide; FM, fibromyalgia; KO, knock out; OA, osteoarthritis; OE, overexpression; PGE2, prostaglandin E2; RA, rheumatoid arthritis; TMJ, temporomandibular joint disorder; TNF, tumour necrosis factor.