Dexmedetomidine as an Adjuvant Analgesic for Intractable Cancer Pain

Roberts, Seth B.; Wozencraft, Colin P.; Coyne, Patrick; Smith, Thomas J.

doi:10.1089/jpm.2010.0235

Cited by 41 publications

(24 citation statements)

References 13 publications

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“…A retrospective study examining the clinical use of antidepressants and breast cancer development found an association between DMI and increased breast cancer risk (42), consistent with the pro-tumor growth effect shown here. DEX is employed as a sedative to treat cancer pain, adding urgency to delve further into the mechanisms underlying chronic DEX treatment and increased tumor growth and metastasis (43, 44). Finally, our results with DMI and elevated synaptic NE imply a balance between pro-metastatic effects of α 2 -AR and anti-metastatic ß-AR with increased NE release.…”

Section: Discussionmentioning

confidence: 99%

The Antidepressant Desipramine and α2-Adrenergic Receptor Activation Promote Breast Tumor Progression in Association with Altered Collagen Structure

Szpunar

Burke

Dawes

et al. 2013

Cancer Prevention Research

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Emotional stress activates the sympathetic nervous system (SNS) and release of the neurotransmitter norepinephrine (NE) to promote breast tumor pathogenesis. We demonstrate here that the metastatic mammary adenocarcinoma cell line 4T1 does not express functional adrenergic receptors (AR), the receptors activated by NE, yet stimulation of AR in vivo altered 4T1 tumor progression in vivo. Chronic treatment with the antidepressant desipramine (DMI) to inhibit NE reuptake increased 4T1 tumor growth but not metastasis. Treatment with a highly-selective α2-AR agonist, dexmedetomidine (DEX), increased tumor growth and metastasis. Neither isoproterenol, a ß-AR agonist, nor phenylephrine, an α1-AR agonist, altered tumor growth or metastasis. Neither DMI- nor DEX-induced tumor growth was associated with increased angiogenesis. In DMI-treated mice, tumor VEGF, IL-6, and the pro-metastatic chemokines RANTES, M-CSF, and MIP-2 were reduced. Tumor collagen microstructure was examined using second harmonic generation (SHG), a non-absorptive optical scattering process to highlight fibrillar collagen. In DMI- and DEX-treated mice, but not ISO-treated mice, tumor SHG was significantly altered without changing fibrillar collagen content, as detected by immunofluorescence. These results demonstrate that α2-AR activation can promote tumor progression in the absence of direct sympathetic input to breast tumor cells. The results also suggest that SNS activation may regulate tumor progression through alterations in the extracellular matrix, with outcome dependent on the combination of AR activated. These results underscore the complexities underlying SNS regulation of breast tumor pathogenesis, and suggest that the therapeutic use of AR blockers, tricyclic antidepressants, and AR agonists must be approached cautiously in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

The Antidepressant Desipramine and α2-Adrenergic Receptor Activation Promote Breast Tumor Progression in Association with Altered Collagen Structure

Szpunar

Burke

Dawes

et al. 2013

Cancer Prevention Research

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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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“…It is evolving as an adjuvant analgesic, both as intravenous and intrathecal infusion, in cancer pain refractory to multiple treatment modalities. [6162]…”

Section: Perioperative Usementioning

confidence: 99%