The dynamic relationship between mu and kappa opioid receptors in body temperature regulation

Chen, Xiaohong; McClatchy, Daniel B.; Geller, Ellen B.; Tallarida, Ronald J.; Adler, Martin W.

doi:10.1016/j.lfs.2005.04.084

Cited by 25 publications

(19 citation statements)

References 23 publications

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“…Similar results after central injection of CTAP or nor-binaltorphimine (nor-BNI), a -opioid-receptor antagonist, were also observed by Ghosh et al (26). Recently, Chen et al (18) also observed that, at low doses, opioid antagonists did not cause any change in T b . However, at higher doses, nor-BNI induced hypothermia and CTAP induced hypothermia and these effects could be blocked by CTAP and nor-BNI, respectively.…”

Section: Discussionsupporting

confidence: 70%

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Fraga

Machado²,

Fernandes³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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This study evaluated the participation of -opioid-receptor activation in body temperature (T b) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid -receptor-antagonist cyclic D-Phe-Cys-Try-DTrp-Arg-Thr-Pen-Thr-NH2 (CTAP; 0.1-1.0 g) reduced fever induced by LPS (5.0 g/kg) but did not change Tb at ambient temperatures of either 20°C or 28°C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0 -10.0 mg/kg, 3.0 -30.0 g, and 1-100 ng, respectively) produced a dose-dependent increase in Tb. Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 g icv) reduced the fever induced by intracerebroventricular administration of TNF-␣ (250 ng), IL-6 (300 ng), CRF (2.5 g), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF2␣ (500.0 ng) but not the fever induced by IL-1␤ (3.12 ng) or PGE2 (125.0 ng) or the second phase of the fever induced by PGF2␣. Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE2 levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1␤ and prostaglandins) recruit the opioid system to cause a -receptor-mediated fever. prostaglandin independent; body temperature; morphine; CTAP THE REGULATION OF BODY TEMPERATURE (T b ) is under the control of a hierarchy of neuronal structures that must first integrate afferent and central information before activating appropriate physiological and behavioral responses. In mammals, T b is regulated with considerable precision, normally varying by only a few degrees Celsius. This is an important adaptation because most biochemical and physiological processes are temperature dependent. In some conditions, adjustments of T b are beneficial. During infection, an increase in T b (fever) enhances immunologic responses and facilitates recovery and survival of an individual (34). In other conditions (such as during hypoxia), a decrease in T b is also beneficial because lower T b increases survival, primarily through a reduction in metabolic rate (13,38). The preoptic area of anterior hypothalamus (POA-AH) is one of the major neuronal structures involved in the control of T b . In addition to receiving afferent input from peripheral thermoreceptors, the POA-AH responds to central changes in hypothalamic temperature (10).Fever is characterized as a controlled elevation in the thermal set point, which is induced initially by exogenous pyrogens. These exogenous pyrogens induce the synthesis and release of a number of endogenous pyrogens, including IL-1␤, TNF...

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Section: Discussionsupporting

confidence: 70%

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Fraga

Machado²,

Fernandes³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…But fortunately, a new class of peripherally restricted kappa agonists (PRKAs), whose access to the brain is restricted by the blood brain barrier, 26 are in development for management of peripheral pain disorders. KNDy neurons reside in the arcuate (or infundibular) nucleus, an area of the hypothalamus which lies at the junction of the blood brain barrier.…”

Section: Introductionmentioning

confidence: 99%

κ Agonists as a novel therapy for menopausal hot flashes

et al. 2015

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Objective Postmenopausal hot flash etiology is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing Kisspeptin, Neurokinin B, and Dynorphin (KNDy neurons), located adjacent to the thermoregulatory center, regulate pulsatile secretion of GnRH and LH. Dynorphin may inhibit this system by binding kappa opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effect of a kappa agonist (KA).Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate-severe hot flashes, ages 48-60 years, were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all 3 interventions: placebo, standard Pentazocine/Naloxone (50/0.5 mg) or low-dose Pentazocine/Naloxone (25/0.25 mg). In an inpatient research setting, each participant received the 3 interventions, in randomized order, on 3 separate days. On each day, an intravenous catheter was inserted for luteinizing hormone (LH) blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results Mean hot flash frequency 2-7 hours following therapy initiation was lower than that for placebo (KA standard-dose: 4.75 ± 0.67; KA low-dose: 4.50 ± 0.57; and placebo: 5.94 ± 0.78 hot flashes/5 hours; p =0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some, but not all women. Conclusions This pilot suggests that kappa agonists may affect menopausal vasomotor symptoms.

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“…The effect of fentanyl upon skin impedance probably would have been even more evident without these cortical influences. An interaction with opiate-induced effects such as nausea, thoracic rigidity, and influence on thermoregulation [41] cannot be excluded. In an intraoperative study involving 11 patients, Storm and colleagues have postulated that the analgesic effect of a general anaesthesia can be determined through measurements of the skin conductance [42].…”

Section: Discussionmentioning

confidence: 99%

Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

Winterhalter

Münte²,

Gerhard

et al. 2010

Eur J Med Res

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Objective Sympathetic stimulation leads to a change in electrical skin impedance. So far it is unclear whether this effect can be used to measure the effects of anaesthetics during general anaesthesia. The aim of this prospective study is to determine the electrical skin impedance during induction of anaesthesia for coronary artery bypass surgery with fentanyl and etomidate. Methods The electrical skin impedance was measured with the help of an electro-sympathicograph (ESG). In 47 patients scheduled for elective cardiac surgery, anaesthesia was induced with intravenous fentanyl 10 μg/kg and etomidate 0.3 mg/kg. During induction, the ESG (Electrosympathicograph), BIS (Bispectral IndeX), BP (arterial blood pressure) and HR (heart rate) values of each patient were recorded every 20 seconds. The observation period from administration of fentanyl to intubation for surgery lasted 4 min. Results The ESG recorded significant changes in the electrical skin impedance after administration of fentanyl and etomidate(p < 0.05). During induction of anaesthesia, significant changes of BIS, HR and blood pressure were observed as well (p < 0.05). Conclusions The electrical skin impedance measurement may be used to monitor the effects of anesthetics during general anaesthesia.

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The dynamic relationship between mu and kappa opioid receptors in body temperature regulation

Cited by 25 publications

References 23 publications

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Endogenous opioids: role in prostaglandin-dependent and -independent fever

κ Agonists as a novel therapy for menopausal hot flashes

Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

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