Table 1.

Substrate	Thermoregulation	Nociception
Sympathetic nerve	Activates BAT Dilates blood vessels in muscle	Constricts vessels in skin Sensitizes primary afferents to pain
Primary afferent C-fibers	Detects heat in BAT Inhibits thermogenesis Detects heat in muscle and skin	Detects pain in muscle and skin
TRPV1 receptors	Thermodetectors	Sensitize nociceptors
Substance P	Dilates vesssels in periphery Initiates cooling centrally	Sensitizes C-fibers directly Sensitizes indirectly (mast cells)
Nerve growth factor	Supports sympathetic fibers (BAT)	Supports primary afferent C-fibers Increases substance P, TRPV1, etc
Subcortical areas
Parabrachial nucleus:	Receives temperature input	Receives tactile & visceral input
DMH:	On-cells inhibit BAT activity	On-cells support hyperalgesia
Cortical areas
Insula:	Associated with skin temperature variation	Abnormal somesthesis in FMS Autonomic & visceral pain
VMPFC:	Crossroad for temperature Integrates interoceptive information Activated by self-referential processing e.g., angina activates	Crossroad for pain Reduced gray matter in FMS
Amygdala:	Signatures of emotion/thermal regulation Stress responses (e.g. sweating)	Reduced grey matter in FMS

Abbreviations: BAT, Brown adipose tissue; DMH, dorsomedial hypothalamus; FMS, fibromyaglia syndrome; TRP, transient receptor potential cation channel; TRPV1, TR vanilloid receptor-1 or TR potential cation channel subfamily V member-1; VMPFC, ventromedial prefrontal cortex