The Antinociceptive Effects of Intravenous Dexmedetomidine in Colorectal Distension-Induced Visceral Pain in Rats: The Role of Opioid Receptors

Ülger, Fatma; Bozkurt, Ayhan; Bilge, S. Sırrı; İlkaya, Fatih; Dilek, Ahmet; Bostanci, M. Ömer; Çıftçıoğlu, Engin; Güldoğuş, Fuat

doi:10.1213/ane.0b013e3181a9fae2

Cited by 35 publications

(29 citation statements)

References 29 publications

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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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“…Combinations of NSAIDs, paracetamol, and opioids are likely to be at least additive if not synergistic [241]. Dexmedetomidine, an alpha-2 antagonist, inhibited visceromotor responses to colorectal distention [273]. In the same manner, tricyclic antidepressants and serotonin norepinephrine reuptake inhibitors could improve visceral pain by increasing norepinephrine neurotransmission.…”

Section: Pharmacologic Management Of Visceral Painmentioning

confidence: 99%

Drug Management of Visceral Pain: Concepts from Basic Research

Davis

2012

Pain Research and Treatment

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Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management.

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“…CRD was used as the model of visceral nociception in awake rats [25, 26]. The distension apparatus was made by the insertion of a latex balloon (6–7 cm in length) to a flexible tygon plastic tubing, with the end of the balloon securely tied to the tube.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, starting at 0 mm Hg, intracolonic pressure was increased in steps (10–20 mm Hg) over about 70–80 s to a final pressure of 80 mm Hg. The first 5 s of EMG activity that has occurred at 80 mm Hg pressure was quantified and used for data analysis [26]. On the day of testing, 4 staircase distensions with 5 min intervals were applied to determine the baseline response prior to drug administration.…”

Section: Methodsmentioning

confidence: 99%

Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats

et al. 2017

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Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration. The opioid receptor antagonist naloxone hydrochloride (NLX) and peripherally restricted opioid receptor antagonist naloxone methiodide (NLXM) were administered intravenously 10 min before tianeptine (10 mg/kg, i.v.). The antinociceptive effect of tianeptine was abolished by NLX (1 and 2 mg/kg, i.v.), but was partially reduced by NLXM (1 and 2 mg/kg, i.v.). A µ-opioid receptor-selective dose (0.03 mg/kg, i.v.) of NLX, but not NLXM, significantly inhibited the antinociceptive effect of tianeptine. Our results suggest that antinociceptive effect of tianeptine on CRD-induced visceral nociception in rats involves the activation of both central and peripheral opioid receptors.

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The Antinociceptive Effects of Intravenous Dexmedetomidine in Colorectal Distension-Induced Visceral Pain in Rats: The Role of Opioid Receptors

Abstract: Our data indicate that IV dexmedetomidine exerts pronounced antinociception against CRD-induced visceral pain and suggest that the antinociceptive effect of dexmedotimidine is mediated in part by opioid receptors, but peripheral alpha(2)-ARs are not involved.

Cited by 35 publications

References 29 publications

Effect of Sedation on Pain Perception

Effect of Sedation on Pain Perception

Drug Management of Visceral Pain: Concepts from Basic Research

Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats

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