Letter on Kobayashi's view of cutaneous thermoreceptors and their role in thermoregulation

Dear Editor-in-Chief, The article by Shigeo Kobayashi reiterates a novel concept for thermoregulation. The concept is provocative, as Kobayashi and colleagues argue against a fundamental protocol of the canonical thermoregulatory control scheme, namely that temperature is measured and encoded by thermal sensors to provide input for the homeostatic control of body temperature. Classical models of thermoregulation are envisioned in terms of an “engineering-style” central controller that receives, decodes and compares afferent temperature information to a reference signal (set-point) as a basis for actuating a coordinated set of effector responses that efficiently, even “wisely,” defend normothermia in the face of thermal challenges. This classical model localizes the “comparator” to the central nervous system (CNS). By contrast, Kobayashi proposes that temperature-sensitive receptor molecules (thermo-TRP channels) located in cutaneous nerve endings are the actual comparators, being triggered at characteristic threshold temperatures so as to generate error inputs that actuate CNSmediated effector responses. This model both precludes requirements for temperature encoding-decoding and thermoeffector coordination via a discrete CNS comparator. Accordingly, Kobayashi has repositioned the ‘thermostat’ from the brain to myriad ‘thermostats’ residing in the interface with the thermal environment. Moreover, according to this model, input from the thermoreceptors is conveyed to other brain areas to evoke temperature sensation (e.g., “cold in the skin”). While Kobayashi’s model is focused on thermoregulation, in a broader sense it also challenges the dominant model of how homeostasis orchestrates the seemingly well-coordinated and energetically efficient effector responses that stabilize a wide variety of regulated variables, at least in the context of “naturalistic” challenges. However, we contend that the accelerating presence of “non-naturalistic” challenges such as drugs of abuse and hyper-palatable refined calories has unmasked the truer nature of biobehavioral regulation. According to the homeostatic perspective, when experimental evidence or clinical data reveal persistent effector states that are poorly coordinated, inefficient or maladaptive, the problem reflects one or more defects located somewhere along the homeostatic negative feedback-CNS controller-actuator-effector axis. Yet even when “broken,” this scheme would actually tend to favor a coordinated set of effector states; i.e., behavioral and autonomic effectors would promote the same outcome. We have argued that a host of pathological regulatory states (drug addiction, obesity, type-2 diabetes, depression) are more readily interpreted in terms of a regulatory model that involves a scheme of distributed control whose elements are relatively independent. Effector independence would be masked in the face of the evolutionarily-based homeostatic challenges that selected for overall system behavior, yet provide a basis for the elaboration of dis-coordinated actions in the face of challenges that were rare or nonexistent during the evolutionary selection for biobehavioral control systems such as persistently excess calories, cocaine and unremitting psychological stress. The allostatic alternative takes into account seminal work, including Satinoff’s model that recast thermoregulatory control in terms of widely distributed semi-autonomous control elements subject to higher CNS-level refinement, and Romanovsky’s model, which compellingly explains ‘setpoint-like’ control as an emergent property of the summated action of independent thermoeffector loops having differing activation thresholds and gains. Importantly, these models were developed in response to experimental evidence for effector dis-coordination under non-naturalistic circumstances, and we have obtained such evidence as well. Kobayashi’s model both complements and extends the ideas presented above, albeit in ways that await critical verification. Kobayashi’s model for thermoregulation is not without some puzzling conjectures and debatable adherences to tradition. How do thermoreceptor potentials that exhibit transient states evoke sustained effector responses? Is skin temperature a primary regulated variable, as proposed by the model, or is it instead a feed-forward trigger for effector Letter on: Kobayashi S. Temperature receptors in cutaneous nerve endings are thermostat molecules that induce thermoregulatory behaviors against thermal load. Temperature 2015; 2(3):346-52; http://dx.doi.org/10.1080/ 23328940.2015.1039190