Individual Differences in Morphine and Butorphanol Analgesia: A Laboratory Pain Study

Abstract

Objective Responses to opioid analgesics are highly variable and the understanding of contributing factors is limited. This laboratory study was designed to examine the contributions of sex and race to inter-individual variability in responses to opioids. Design A randomized, double blind, mixed design was implemented in the evaluation of analgesic response to a μ-opioid agonist and mixed agonist-antagonist, using three well-validated experimental pain assays (thermal, pressure, and ischemic). Subjects Participants included a total of 142 healthy subjects (76M/66F), 119non-Hispanic whites and 23 African Americans. Intervention Three sessions of pain testing were completed prior to and following an intravenous administration of morphine (0.08 mg/kg), butorphanol (0.016 mg/kg), and placebo (saline) in counterbalanced order. Outcome Measures A change score was calculated from the difference between the pre-drug and post-drug values. Three separate change scores (morphine, saline, and butorphanol) were computed for each experimental pain variable. Mixed-model analyses of covariance were performed on analgesic change scores. Results Significant sex differences emerged for pre-drug pain measures with minimal differences for race. Sex differences in opioid analgesia were not demonstrated. However, significant race differences and race X drug interactions emerged for thermal, pressure, and ischemic pain measures. The pattern of results generally indicated that for pressure and ischemic pain, African American subjects showed greater analgesic responses to both medications compared to non-Hispanic whites. For thermal pain threshold, butorphanol but not morphine analgesia was greater for African Americans versus non-Hispanic whites. Conclusions Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia.

An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans

“…Differences in the response to exogenous opioids between ancestral populations have previously been observed (Bayerer et al, 2007;Nielsen et al, 2010). The effect of butorphanol and morphine on certain types of analgesia is greater in African-Americans compared with nonHispanic whites (Sibille et al, 2011). The different genetic backgrounds of African-Americans and European-Americans are likely to contribute to the differential response to opioids observed by Sibille et al (2011).…”

“…The effect of butorphanol and morphine on certain types of analgesia is greater in African-Americans compared with nonHispanic whites (Sibille et al, 2011). The different genetic backgrounds of African-Americans and European-Americans are likely to contribute to the differential response to opioids observed by Sibille et al (2011). Drug metabolism rates between patients of different ancestry have also been associated with genetic variation (Bradford, 2002).…”

Analgesic effect and pharmacological mechanism of fentanyl and butorphanol in a rat model of incisional pain

“…Sibille et al hypothesized that the agonist activity of butorphanol at κ-receptors might functionally have opposite effects on the progressive increase of activity mediated by μ-receptors [33]. In addition, with the increasing dose of fentanyl, it occupied more μ-receptor; in contrary, the number of μ-receptor has been decreased gradually for butorphanol, which showed more obvious μ-receptor antagonism [31,32]. Relevant research has suggested that the combination of butorphanol and pure μ-receptor in clinical application does not produce analgesia effect but reverse analgesic effects, which results in the severity of pain [34].…”

“…Generally, fentanyl is known as a lipid-soluble narcotic with strong μ-receptor agonist, whereas butorphanol has its analgesic and antagonist effects with weak μ-receptor agonist and strong κ-receptor agonist [8,30]. Meanwhile, it is well documented that butorphanol has double agonistic and antagonistic effects on μ-receptor [31,32]. Sibille et al hypothesized that the agonist activity of butorphanol at κ-receptors might functionally have opposite effects on the progressive increase of activity mediated by μ-receptors [33].…”

Efficacy and safety of nonsteroidal anti‐inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo‐controlled study

“…have evaluated the differences in experimentally induced pain perception and threshold between subjects from different ethnicities, with inconsistencies found among populations. Race‐related differences may also exist in patients' responses to pain medications 9, 10. It has previously been demonstrated that a variant of the cytochrome P450 allele, which is predominantly found in Asian populations, can lead to significant alterations in the metabolism of certain nonsteroidal anti‐inflammatory drugs (NSAIDs) 11.…”