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In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED 50 in the 0.5-1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. "On-" and "off-" neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index., (Copyright © 2016 the American Physiological Society.)

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., (Copyright © 2016 the American Physiological Society.)

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., (Copyright © 2014 the American Physiological Society.)

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., (Copyright © 2014 the American Physiological Society.)

Background and Objective: Endoscopic retrogade cholangio-pancreatography (ERCP) is a painful procedure that requires transient analgesia and conscious sedation. Remifentanil an ultrashort, very potent narcotic, is eliminated by plasma esterases, and does not interfere with liver function. It does not accumulate and is free of residual depression. Our aim is to find out if remifentanil can provide safe and effective sedation in ERCP, without undue technical difficulty secondary to sphincter spasm., Patients and Methods: Thirty five patients, ASA I-II and III, scheduled to undergo elective ERCP were divided randomly in two groups: Midazolam-remifentanil group (group I), received remifentanil a loading dose of 0.2 microg/Kg/min over 5 minutes and a maintenance dose of 0.1-0.15 microg/Kg/min to achieve an adequate level of sedation and analgesia. Midazolam-fentanyl group (group II), received intermittent doses of midazolam and fentanyl guided by level of sedation. All patients were premedicated with midazolam 0.05 mg/kg IV, in divided doses as per patient tolerance, before starting the procedure. Sedation was assessed depending on Ramsey scale of sedation. SpO2, blood pressure, heart rate, respiratory rate, dosages of the medications, peroperative amnesia and operative time were recorded. Operator and patient satisfaction were rated on a scale of 1 to 4., Results: There were statistically significant differences in the level of sedation (p = 0.003), patient satisfaction (p = 0.01) and the amount of midazolam used (p < 0.01) in favor of group I. Operator satisfaction was the same in the two groups. There was no statistically significant difference between the two groups regarding the peri-operative amnesia. The technical difficulty (catheterization of ampulla, duration of procedure, need of parasympatholytics...) was comparable in the two groups, as judged by the operator. There was one case of mild desaturation in group I that responded to stimulation. No other respiratory or cardiovascular events were noted., Conclusion: We recommend remifentanil in ERCP. Vigilance, however, must be exercised in titration and supervision of patients.

Objective: Pain management in patients having a subarachnoid haemorrhage was assessed in French intensive care unit of neurosurgical centres., Study Design: Nationwide survey., Methods: A standardized postal questionnaire was sent to senior doctor of every neurosurgical centres in France inquiring pain scores assessment, analgesics used and their routes of administration, centre's opinion about efficacy of pain management., Results: Of the 34 centres, 24 returned completed questionnaires. Fifty four per cent of the centres evaluated pain intensity with a non valid pain score. In the case of patients in the comatose, pain was not evaluated in fifty four per cent of the centres. Paracetamol and morphine were the most currently used analgesics drugs. Morphine was administered subcutaneously by 75% of the centres. Six centres used also PCA. Thirty-seven percent of the centres were reluctant to use opioids and 75% to use NSAIDS., Conclusion: The majority of the centres considered pain management in patient suffering from subarachnoid haemorrhage (SAH) was not optimal and stressed the need to establish a well validated pain rating scale dedicated to SAH patients.