Dear Editor,
We thank Doctor Davis for taking an interest in our publication entitled “Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose” [1]. We make several comments in response.
Doctor Davis may have misunderstood the main thrust of our publication, which was to demonstrate that participants in a buprenorphine maintenance program were hyperalgesic and had no antinociceptive response to high-dose morphine. As discussed in the Methods Section, 1) we did not have access to the participants before they entered the buprenorphine maintenance program and 2) at enrollment into our study, they were pain free, as is the case in many such individuals. Thus, Doctor Davis’ assertion that “what is also missing in this study is a measure of patient affect and patient pain tolerance prior to buprenorphine maintenance” is not relevant. Furthermore, his reference to chronic pain (endometriosis, low-grade inflammation from a vaccine, pain response in analgesic trials) is also not relevant to our paper.
Doctor Davis seems to be critical of our choice of experimental pain models. We refer him to a review entitled “Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs” [2] in which the authors recommend using suprathreshold pain stimuli, of which the cold pressor test is one such method. Doctor Davis makes reference to a publication by Cimpean and David [3]. The measure of pain tolerance in that paper is different from ours (they used total time in ice water minus time to reach threshold rather than the more usual total time in ice water, as in our paper). We would find it difficult to make valid comparisons between our methods and those used by these authors.
We consider our choice of title for this paper appropriate, as it adequately describes our subjects, with the inference that high-dose morphine would not be of particular use in these subjects if they are experiencing acute pain and have opioid-induced hyperalgesia (which our subjects did). Importantly, our findings are in accordance with those of MacIntyre et al. (reference 25 in our publication [4]) and provide a plausible mechanistic explanation for the very poor analgesic response to high-dose opioids experienced by their patients in a clinical setting.
Funding sources: This study was supported by National Institute on Drug Abuse grant R01 DA 13706-02.
References
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