Transdermal Fentanyl Reduces Pain and Improves Functional Activity in Neuropathic Pain States

Agarwal, Shefali; Polydefkis, Michael; Block, Brian M.; Haythornthwaite, Jennifer A.; Raja, Srinivasa N.

doi:10.1111/j.1526-4637.2006.00246.x

Cited by 35 publications

(30 citation statements)

References 31 publications

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“…After one week of fentanyl administration, locomotor activity increased for all fentanyl-treated animals. These results suggest that sedation may not be a major concern with chronic fentanyl administration, and similar results have been observed in clinical setting with human patients (Agarwal et al 2007). Interestingly, activity levels continued to increase throughout the drug treatment period, and these increases in activity were lowest in the oldest animals (although by week 4 activity levels were similar across ages), suggesting that opioids have a diminished effect with increasing age.…”

Section: Discussionsupporting

confidence: 86%

Thermal sensitivity across ages and during chronic fentanyl administration in rats

2013

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Rationale Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Results Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.

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Section: Discussionsupporting

confidence: 86%

Thermal sensitivity across ages and during chronic fentanyl administration in rats

2013

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“…It has been reported that the therapeutic use of opioids can be associated with altered cognition and impaired psychomotor function, particularly when first administered (Chapman et al, 2002; Kamboj et al, 2005). However, some studies reach the opposite conclusion when these medications are used long-term (Agarwal et al, 2007; Gaertner et al, 2006), even with reports of improved cognition (Lorenz et al, 1997; Panjabi et al, 2008). Concordantly, Brown and colleagues (Brown et al, 2006) developed a regression model in which psychological factors and pain severity predicted the decline in cognitive function better than specific opioid medications or daily opioid dose.…”

Section: Discussionmentioning

confidence: 99%

Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: A randomized cross-over trial

Wilsey

Fishman

et al. 2009

Pharmacology Biochemistry and Behavior

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Background Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects. Methods We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity). Results Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high. Conclusions Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

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“…Khallouk-Bousselmame & Costentin, 1994; Powell & Holtzman, 2001; Rauhala et al, 1995; Trujillo et al, 2004). Clinically, extended fentanyl administration increases activity, although it is unclear if this is a direct effect of fentanyl or a by-product of mitigation of chronic pain in these patients (Agarwal et al, 2007). Age-related decreases in rotarod performance were maintained throughout all phases of drug/saline administration, however fentanyl did not influence performance.…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic fentanyl administration on physical performance of aged rats

Mitzelfelt

DuPree

Seo

et al. 2011

Experimental Gerontology

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There is growing concern over the increasing use of opioids to treat chronic pain in the elderly primarily because of the potential increased sensitivity to the adverse side effects. Here, we use a preclinical model (male Brown Norway X F344 rats aged 12, 18, 24, and 30 months) to describe the outcome of chronic fentanyl administration (1.0 mg/kg/day) on various physiological and behavioral measures. Continuous fentanyl administration resulted in an initial decrease in food consumption, followed by the development of tolerance to this effect over a 4-week period and a subsequent increase in food consumption during withdrawal. This change in food consumption was associated with decreases in body weight (predominantly due to a loss of fat mass) that was maintained through early withdrawal. After one month of withdrawal, only the 12-month old animals had fully regained body weight. Fentanyl administration resulted in a decrease in grip strength and an increase in locomotor activity that did not differ across age groups. There was no effect of fentanyl administration on rotarod performance. These results demonstrate that while there is a delayed recovery of body mass with age, the observed changes in behavioral responses are uniform across ages.

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Transdermal Fentanyl Reduces Pain and Improves Functional Activity in Neuropathic Pain States

Abstract: Overall, there was a significant reduction in pain intensity and increase in activity in neuropathic pain patients treated with transdermal fentanyl.

Cited by 35 publications

References 31 publications

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: A randomized cross-over trial

Effects of chronic fentanyl administration on physical performance of aged rats

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