Thermo-mechanical pain: the signaling role of heat dissipation in biological tissues

Abstract

Mechanical algesia is an important process for the preservation of living organisms, allowing potentially life-saving reflexes or decisions when given body parts are stressed. Yet, its various underlying mechanisms remain to be fully unraveled. Here, we quantitatively discuss how the detection of painful mechanical stimuli by the human central nervous system may, partly, rely on thermal measurements. Indeed, most fractures in a body, including microscopic ones, release some heat, which diffuses in the surrounding tissues. Through this physical process, the thermo-sensitive TRP proteins, that translate abnormal temperatures into action potentials, shall be sensitive to damaging mechanical inputs. The implication of these polymodal receptors in mechanical algesia has been regularly reported, and we here provide a physical explanation for the coupling between thermal and mechanical pain. In particular, in the human skin, we show how the neighboring neurites of a broken collagen fiber can undergo a sudden thermal elevation that ranges from a fraction to tens of degrees. As this theoretical temperature anomaly lies in the sensibility range of the TRPV3 and TRPV1 cation channels, known to trigger action potentials in the neural system, a degree of mechanical pain can hence be generated.

Heat emitting damage in skin: a thermal pathway for mechanical algesia

“…Note that, consistently, our estimation of φ is inline with what we elsewhere reported for the tear of another fibrous tissue of biological origin, that is, paper [9], where φ was about 10%. The here measured thermal anomalies are however bigger than those that we recently theorised, when the here discussed pain pathway was first proposed [17]. In this former theoretical study, it was suggested that these anomalies should be on the edge of the TRPs sensitivity and thus relevant to hyperalgesia only rather than to direct algesia as well.…”

“…6). The pixel size of our measurement (∼ 85 µm) was about half an order of magnitude bigger than the typical distance between two neurites (∼ 20 µm [17,27]). It was also almost two orders of magnitude bigger than the length scale l, where the heat is dissipated (here inverted to be in the micrometer range, which is similar to the size of the skin fibers, with two different methods, i.e., with Eqs.…”

“…To understand how significant would any heat anomaly be in terms of algesia (pain), it is important to compare the time and space resolutions of our (infrared) thermal measurements to the time and space sensibility of the human nervous system. Based on microscopic observations [27] of the density D n of neurites in the human epidermis (i.e., the body extension of neurons), D n ∼ 2000 mm -2 , one can broadly estimate [17] the nom-FIG. 2.…”

“…These effects notably include the brittleness of matter [9][10][11][12][13] or the instability of some seismic faults (e.g., [14][15][16]) through various thermal weakening phenomena. Recently, we have also suggested a theory [17] that the damage-induced heat in biological tissues could be responsible for a degree of mechanical pain in the human body. Indeed, should the heat dissipation be large enough, it may be detected by the thermo-sensitive nociceptors of sensory neurons, the so-called TRPs proteins, and thus may trigger action potentials (i.e., electrochemical signals) in the nervous system.…”

“…Their ability to gate ions through cells' membranes [20] is temperature dependent, and different TRP types react to different temperature ranges. In particular, the role of TRPV3 and TRPV1 was considered [17] * tom.vincent-dospital@fys.uio.no in the detection of fracture induced heat. The former (TRPV3) is sensitive to temperatures in the normal biological range (i.e., 30 to 40 • C), making it likely responsible for the feeling of warmth, and the latter (TRPV1) starts to activate at more painful temperatures above about 43 • C (e.g., [18,19]).…”