Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage

Beneficial effects of massage on tired muscles work through anti-inflammatory and mitochondrial biogenesis pathways. The Mechanism of Massage Massage is a popular treatment—both for its putative healing properties and because it feels good—but is not among the usual tools of physicians. To validate its usefulness and understand how massage affects muscles in biomedical terms, Crane and his colleagues have documented the biological changes that massage evokes in the leg muscles of 11 young men who had just pushed themselves to exhaustion with heavy exercise. The exercise itself caused massive changes in gene expression, but after 10 min of massage, signaling pathways responsive to mechanical stresses were activated. Massage reduced signs of inflammation, and massaged muscle cells were better able to make new mitochondria—promoting faster recovery from exercise-induced muscle damage. Massage stretches and pulls muscles and, as one might expect, the authors found that mechanosensory sensors focal adhesion kinase–1 and its downstream effectors extracellular signaling kinases 1 and 2 were activated, as revealed by their increased phosphorylation. Several hours after massage, another downstream target of this pathway, PGC-1α, shifted into the nucleus, where it in turn activated transcription of its own targets COX7B and ND1. This set of responses indicated that additional mitochondria were forming, presumably accelerating healing of the muscle. Massage also altered the behavior of NFκB, causing less of this key inflammatory mediator to accumulate in the nucleus. Consequently, the NFκB-regulated heat shock proteins and immune cytokines interleukin-6 and tumor necrosis factor–α were less active, a sign of less cellular stress and inflammation. But one oft-repeated idea turned out not to be true. As others have shown, massage did not help clear lactic acid from tired muscles. And glycogen levels were also unchanged. Now that we know something about how massage heals, perhaps we will soon get some idea of why it is so enjoyable. Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal–regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α)], and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor–α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis.