Fig. 12

Neurochemical mechanisms for the development of DOMS. The starting point of this schema is based on the report by Boix et al. [92] that a bradykinin-like substance (Arg-bradykinin) is produced and released from blood vessels by the adenosine released by muscle contraction [148, 149]. Arg-bradykinin binds to and activates the B2 bradykinin receptor (B2R) in muscle cells to stimulate NGF production. NGF sensitizes C-fibers only when high concentrations are used, and both Aδ- and C-fibers when a low mix is used or in DOMS involving TRPV1 and ASIC3. In addition, the activation of B2R upregulates COX-2. Another route involves the upregulation of COX-2 in muscle fibers, resulting in increased production of prostaglandin (PG) E2. PGE2 rapidly spreads from the cells and binds to the EP2 receptor [150] to stimulate GDNF production. GDNF sensitizes nociceptors (Aδ-fibers only when high concentration was used, and both Aδ- and C-fibers when low mix was used or in DOMS) involving TRPV4 and ASIC3. A synergistic interaction has been observed between NGF and GDNF at the primary afferent level. The mechanism of this synergistic interaction is open to future studies