Effects of dexmedetomidine on conditioned pain modulation in humans

Baba, Yoshifumi; Kohase, Hikaru; Oono, Yuka; Fujii-Abe, Keiko; Arendt-Nielsen, Lars

doi:10.1002/j.1532-2149.2012.00129.x

Cited by 36 publications

(29 citation statements)

References 43 publications

(78 reference statements)

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“…It is used for procedural sedation, as adjuvant hypnotic during surgery and mechanically ventilated patients in an intensive care setting. There are some preclinical reports 50 to suggest dexmedetomidine has analgesic effects, some clinical evidence on its inhibition of pain conditioning 51 and as adjuvant analgesic for intractable cancer pain 52 but its direct effects on pain remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sedation on Pain Perception

Frölich

Zhang

Ness³

2013

Anesthesiology

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Background Sedation or anesthesia is used to facilitate many cases of an estimated 45 million diagnostic and therapeutic medical procedures in the United States. Preclinical studies have called attention to the possibility that sedative hypnotic drugs can increase pain perception but it remains unclear whether this observation holds true in humans and whether pain-modulating effects are agent specific or characteristic of intravenous sedation in general. Methods To study this important clinical question, we recruited 86 healthy volunteers and randomly assigned them to receive one of three sedative drugs; midazolam, propofol or dexmedetomidine. We asked participants to rate their pain in response to four experimental pain tasks (cold, heat, ischemic or electrical pain) before and during moderate sedation. Results Midazolam increased cold, heat and electrical pain perception significantly (10-point pain rating scale change = 0.82 ± 0.29, mean ± SEM). Propofol reduced ischemic pain and dexmedetomidine reduced both cold and ischemic pain significantly (−1.58 ± 0.28, mean ± SEM). We observed a gender-by-race interaction for dexmedetomidine. In addition to these drug specific effects, we observed gender effects on pain perception; females rated identical experimental pain stimuli higher than males. We also noted racedrug interaction effects for dexmedetomidine with higher doses of drug needed to sedate Caucasians when compared to African-Americans. Conclusions The results of our study call attention to the fact that intravenous sedatives may increase pain perception. The effect of sedation on pain perception is agent and pain type specific. Knowledge of these effects provides a rational basis for analgesia and sedation to facilitate medical procedures.

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Section: Discussionmentioning

confidence: 99%

Effect of Sedation on Pain Perception

Frölich

Zhang

Ness³

2013

Anesthesiology

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“…Alpha2 agonists inhibit CPM, in a dose-dependent manner. 4 The ability of CPM to predict analgesic effect was examined in healthy controls by Eisenberg et al, 22 finding that CPM did not predict efficacy of oxycodone, whereas heat pain thresholds (HPT) and TS did. Use of CPM in prediction of analgesic effect was reported by these authors, as described above.…”

Section: Pharmacological and Therapeutic Applicationsmentioning

confidence: 99%

Role of endogenous pain modulation in chronic pain mechanisms and treatment

Yarnitsky

2015

Pain

266

214

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Development and application of psychophysical test paradigms to assess endogenous pain modulation in healthy controls and in patients yielded large body of data over the last 2 decades. These tests can assist in predicting pain acquisition, in characterizing pain syndromes and related dysfunctions of pain modulation, and in predicting response to treatment. This chapter reviews the development of thought on pain modulation in the clinical setup, focusing on conditioned pain modulation, and update on accumulated data regarding the mechanism, protocols of administration, and applications in the clinic.

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“…Therefore the analgesic effect of conditioned pain modulation may involve the activation of the pain-inhibiting pathways arising from the LC. Indeed, duloxetine, a noradrenaline reuptake inhibitor which potentiates noradrenergic neurotransmission, enhances conditioned pain modulation [Yarnitsky et al, 2012 (noxious cold)], whereas dexmedetomidine, an α 2 -adrenoceptor agonist which reduces LC activity, inhibits it [Baba et al, 2012 (electric tooth pulp stimulation)]. Conditioned pain modulation is a form of sensory gating, and it may be analogous to “prepulse inhibition,” when a weak stimulus applied within a time window attenuates the effect of a strong stimulus (Perlstein et al, 2001).…”

Section: Modulation Of Pain By the Lcmentioning

confidence: 99%

Modulation of physiological reflexes by pain: role of the locus coeruleus

Szabadi

2012

Front. Integr. Neurosci.

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The locus coeruleus (LC) is activated by noxious stimuli, and this activation leads to inhibition of perceived pain. As two physiological reflexes, the acoustic startle reflex and the pupillary light reflex, are sensitive to noxious stimuli, this review considers evidence that this sensitivity, at least to some extent, is mediated by the LC. The acoustic startle reflex, contraction of a large body of skeletal muscles in response to a sudden loud acoustic stimulus, can be enhanced by both directly (“sensitization”) and indirectly (“fear conditioning”) applied noxious stimuli. Fear-conditioning involves the association of a noxious (unconditioned) stimulus with a neutral (conditioned) stimulus (e.g., light), leading to the ability of the conditioned stimulus to evoke the “pain response”. The enhancement of the startle response by conditioned fear (“fear-potentiated startle”) involves the activation of the amygdala. The LC may also be involved in both sensitization and fear potentiation: pain signals activate the LC both directly and indirectly via the amygdala, which results in enhanced motoneurone activity, leading to an enhanced muscular response. Pupil diameter is under dual sympathetic/parasympathetic control, the sympathetic (noradrenergic) output dilating, and the parasympathetic (cholinergic) output constricting the pupil. The light reflex (constriction of the pupil in response to a light stimulus) operates via the parasympathetic output. The LC exerts a dual influence on pupillary control: it contributes to the sympathetic outflow and attenuates the parasympathetic output by inhibiting the Edinger-Westphal nucleus, the preganglionic cholinergic nucleus in the light reflex pathway. Noxious stimulation results in pupil dilation (“reflex dilation”), without any change in the light reflex response, consistent with sympathetic activation via the LC. Conditioned fear, on the other hand, results in the attenuation of the light reflex response (“fear-inhibited light reflex”), consistent with the inhibition of the parasympathetic light reflex via the LC. It is suggested that directly applied pain and fear-conditioning may affect different populations of autonomic neurones in the LC, directly applied pain activating sympathetic and fear-conditioning parasympathetic premotor neurones.

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Effects of dexmedetomidine on conditioned pain modulation in humans

Abstract: The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM.

Cited by 36 publications

References 43 publications

Effect of Sedation on Pain Perception

Effect of Sedation on Pain Perception

Role of endogenous pain modulation in chronic pain mechanisms and treatment

Modulation of physiological reflexes by pain: role of the locus coeruleus

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