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In humans, temperature sensation enters the spinal cord along the axons of Lissauer's tract that synapse on second order neurons in grey matter of the dorsal horn, one or two vertebral levels up. The axons of these second order neurons then decussate, joining the spinothalamic tract as they ascend to neurons in the ventral posterolateral nucleus of the thalamus.








Warm and cold receptors play a part in sensing innocuous environmental temperature. Temperatures likely to damage an organism are sensed by sub-categories of nociceptors that may respond to noxious cold, noxious heat or more than one noxious stimulus modality (i.e., they are polymodal). The nerve endings of sensory neurons that respond preferentially to cooling are found in moderate density in the skin but also occur in relatively high spatial density in the cornea, tongue, bladder, and facial skin. The speculation is that lingual cold receptors deliver information that modulates the sense of taste; i.e. some foods taste good when cold, while others do not.

Mechanism of transduction[edit]

This area of research has recently received considerable attention with the identification and cloning of the Transient Receptor Potential (TRP) family of proteins. The transduction of temperature in cold receptors is mediated in part by the TRPM8 channel. This channel passes a mixed inward cationic (predominantly carried by Na+ ions although the channel is also permeable to Ca2+) current of a magnitude that is inversely proportional to temperature. The channel is sensitive over a temperature range spanning about 10-35°C. TRPM8 can also be activated by the binding of an extracellular ligand. Menthol can activate the TRPM8 channel in this way. Since the TRPM8 is expressed in neurons whose physiological role is to signal cooling, menthol applied to various bodily surfaces evokes a sensation of cooling. The feeling of freshness associated with the activation of cold receptors by menthol, particularly those in facial areas with axons in the trigeminal (V) nerve, accounts for its use in numerous toiletries including toothpaste, shaving lotions, facial creams and the like.

Another molecular component of cold transduction is the temperature dependence of so-called leak channels which pass an outward current carried by potassium ions. Some leak channels derive from the family of two-pore (2P) domain potassium channels. Amongst the various members of the 2P-domain channels, some close quite promptly at temperatures less than about 28°C (e.g. TRAAK, TREK). Temperature also modulates the activity of the Na+/K+-ATPase. The Na+/K+-ATPase is a P-type pump that extrudes 3Na+ ions in exchange for 2K+ ions for each hydrolytic cleavage of ATP. This results in a net movement of positive charge out of the cell, i.e. a hyperpolarizing current. The magnitude of this current is proportional to the rate of pump activity.

It has been suggested that it is the constellation of various thermally sensitive proteins together in a neuron that gives rise to a cold receptor.[2] This emergent property of the neuron is thought to comprise, the expression of the aforementioned proteins as well as various voltage-sensitive channels including the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel and the rapidly activating and inactivating transient potassium channel (IKA).


  1. ^ Darian-Smith, Ian; Johnson KO; LaMotte C; Shigenaga Y; Kenins P; Champness P (1979). "Warm fibers innervating palmar and digital skin of the monkey: responses to thermal stimuli.". Journal of Neurophysiology 42 (5): 1297–1315. PMID 114608. 
  2. ^ Viana, Felix; la Peña E; Belmonte C (2002). "Specificity of cold thermotransduction is determined by differential ionic channel expression.". Nature Neuroscience 5 (3): 254–260. doi:10.1038/nn809. PMID 11836533.