The tail and paws in rodents are heat exchangers involved in the maintenance of core body temperature (T(core)). They are also the most widely used target organs to study acute or chronic "models" of pain. We describe the fluctuations of vasomotor tone in the tail and paws in conditions of thermal neutrality and the constraints of these physiological processes on the responses to thermal nociceptive stimuli, commonly used as an index of pain. Skin temperatures were recorded with a calibrated thermal camera to monitor changes of vasomotor tone in the tail and paws of awake and anesthetized rats. In thermoneutral conditions, the sympathetic tone fluctuated at a rate of two to seven cycles/h. Increased mean arterial blood pressure (MAP; ∼46 mmHg) was followed by increased heart rate (HR; ∼45 beats/min) within 30 s, vasoconstriction of extremities (3.5-7°C range) within 3-5 min, and increased T(core) (∼0.7°C) within 6 min. Decreased MAP was followed by opposite events. There was a high correlation between HR and T(core) recorded 5-6 min later. The reaction time of the animal's response to a radiant thermal stimulus-heat ramp (6°C/s, 20 mm(2) spot) generated by a CO2 laser-directed to the tail depends on these variations. Consequently, the fluctuations in tail and paw temperature thus represent a serious confound for thermal nociceptive tests, particularly when they are conducted at thermal neutrality.

In thermal neutral condition, rats display cyclic variations of the vasomotion of the tail and paws, synchronized with fluctuations of blood pressure, heart rate, and core body temperature. "On-" and "off-" cells located in the rostral ventromedial medulla, a cerebral structure implicated in somatic sympathetic drive, 1) exhibit similar spontaneous cyclic activities in antiphase and 2) are activated and inhibited by thermal nociceptive stimuli, respectively. We aimed at evaluating the implication of such neurons in autonomic regulation by establishing correlations between their firing and blood pressure, heart rate, and skin and core body temperature variations. When, during a cycle, a relative high core body temperature was reached, the on-cells were activated and within half a minute, the off-cells and blood pressure were depressed, followed by heart rate depression within a further minute; vasodilatation of the tail followed invariably within ∼3 min, often completed with vasodilatation of hind paws. The outcome was an increased heat loss that lessened the core body temperature. When the decrease of core body temperature achieved a few tenths of degrees, sympathetic activation switches off and converse variations occurred, providing cycles of three to seven periods/h. On- and off-cell activities were correlated with inhibition and activation of the sympathetic system, respectively. The temporal sequence of events was as follows: core body temperature → on-cell → off-cell ∼ blood pressure → heart rate → skin temperature → core body temperature. The function of on- and off-cells in nociception should be reexamined, taking into account their correlation with autonomic regulations.

Thermal neutrality in rodents is achieved by large cyclic variations of the sympathetic drive of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Given the pivotal functional role of rostral ventromedial medulla (RVM) in nociception and rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, we aimed at circumscribing the brainstem regions that are the source of premotor afferents to sympathetic preganglionic neurons that control the vasomotor tone of the tail and hind paws. A thermometric infrared camera recorded indirectly the vasomotor tone of the tail and hind paws. During the control period, the rat was maintained in vasoconstriction by preserving a stable, homogeneous, and constant surrounding temperature, slightly below the core temperature. The functional blockade of the RVM/rMR by the GABAA receptor agonist muscimol (0.5 nmol, 50 nl) elicited an extensive increase of the temperature of the paws and tail, associated with a slight decrease of blood pressure and heart rate. Both the increased heat loss through vasodilatation and the decrease heart-induced heat production elicited a remarkable reduction of the central temperature. The effective zones were circumscribed to the parts of the RVM/rMR facing the facial nucleus. They match very exactly the brain regions often described as specifically devoted to the control of nociception. Our data support and urge on the highest cautiousness regarding the interpretation of results aimed at studying the effects of any pharmacological manipulations of RVM/rMR with the usual tests of pain.