Sex-related psychological predictors of baseline pain perception and analgesic responses to pentazocine
Introduction
Sex-related influences on experimental pain responses have been widely reported. Both qualitative and quantitative reviews of the experimental pain literature have concluded that women consistently exhibit more robust perceptual responses to laboratory pain than men, and these differences are moderate in magnitude (Berkley, 1997, Fillingim and Maixner, 1995, Riley et al., 1998). More recently, evidence of sex differences in responses to opioid analgesics has emerged (Craft, 2003, Kest et al., 2000); however, the findings are variable across studies (Fillingim and Gear, 2004). For example, with regards to morphine and post-operative pain, evidence of greater analgesia among women (Miaskowski and Levine, 1999, Chia et al., 2002), greater analgesia among men (Cepeda and Carr, 2003), and equivalent analgesia across sexes has been reported (Gordon et al., 1995). Laboratory studies have demonstrated more robust analgesic responses to μ-opioid agonists (e.g., morphine, hydromorphone) among women compared to men (Sarton et al., 2000, Zacny, 2002). Also, women showed greater analgesic responses to κ-agonist-antagonist medications (pentazocine, nalbuphine, and butorphanol) following oral surgery (Gear et al., 1996a, Gear et al., 1996b, Gordon et al., 1995), while we recently reported no sex differences in the effects of pentazocine (a κ-agonist-antagonist) on experimental pain responses (Fillingim et al., 2004). Thus, in contrast to the relatively consistent findings regarding basal pain perception, sex differences in opioid analgesic responses vary considerably across studies.
The literature addressing sex differences in pain and analgesia focuses predominantly on quantitative differences; that is, do women and men differ in the amount of pain or analgesia that they display? Of potentially greater importance are qualitative sex differences in pain and analgesia; that is, do certain factors (e.g., genetics, psychological processes) moderate pain and analgesic responses differently in women versus men? Such differences are particularly compelling as they may indicate sex-specific mechanisms underlying individual differences in pain and analgesia. In addition, a better understanding of factors that sex-dependently influence analgesic responses could help clarify the inconsistency of previous findings. We recently reported one such qualitative sex difference, in that the melanocortin-1-receptor gene (MC1R) moderated analgesic responses to pentazocine among women but not men (Mogil et al., 2003).
In addition to genetic factors, psychological variables could be differentially associated with pain and analgesic responses among women and men. For example, the association of anxiety with clinical pain, sensitivity to experimental pain, and treatment-related pain reductions is more robust among men than women (Edwards et al., 2000, Edwards et al., 2003, Fillingim et al., 1996, Jones et al., 2003). Moreover, maladaptive pain coping strategies, such as catastrophizing, have been associated with poorer adjustment to clinical pain and higher sensitivity to experimental pain (Geisser et al., 1992, Sullivan et al., 2001, Sullivan et al., 2004, Thorn et al., 2003). Several investigators have reported higher catastrophizing among women than men (Fillingim et al., 1999, Keefe et al., 2000, Osman et al., 2000), and catastrophizing mediated sex differences in the severity of arthritis pain and pain-related disability (Keefe et al., 2000). However, whether catastrophizing predicts experimental pain perception differently in women and men has not been reported. Moreover, the association of affective factors and catastrophizing to opioid analgesia has not been determined. In order to examine these issues, we assessed positive and negative affect, as well as catastrophizing in a sample of healthy women and men, after which we quantified baseline pain perception and pentazocine analgesia using well-validated experimental pain methodology. We then examined sex-specific associations between these psychological factors and baseline pain perception and analgesia. We recently reported an absence of sex differences in pentazocine analgesia from this data set (Fillingim et al., 2004); therefore, these analyses focus specifically on the association of psychological factors with pain and analgesic responses.
Section snippets
Subjects
Subjects included 49 women and 39 men recruited via posted advertisements. All participants were healthy non-smokers and were free of clinical pain, psychiatric disturbance, substance abuse, or use of centrally acting medications. Subjects refrained from any over-the-counter medication use for at least 24 h prior to testing. Twenty-four (49%) of the women were taking oral contraceptives. Subjects were paid US$ 50 per experimental session for their participation.
Pain testing procedures
The following psychophysical pain procedures were performed before and after drug administration. Pressure and thermal pain were delivered first in counterbalanced order, separated by a 5-min rest period. The tourniquet procedure always occurred last in order to reduce the possibility of carryover effects. Prior to each pain procedure, digitally recorded instructions were played for the subject.
Positive and Negative Affect Scale (PANAS)
The PANAS is a 20-item scale. Respondents indicated the frequency with which they generally experience 10 positive (e.g., “excited”) and 10 negative (e.g., “nervous”) feelings (Watson et al., 1988). This is a well-validated measure of positive and negative affect, and with this instructional set it reflects mood states that are relatively stable over time (Watson et al., 1988, Watson, 1988). It yields two scores, one for positive affect and one for negative affect.
Coping strategies questionnaire (CSQ)
The CSQ is the most commonly
Pain and analgesic responses
Women were slightly older than men and ethnicity was similar across sex, with the majority of participants being white (78.5% White, 8.9% Hispanic, 6.3% African American, and 6.3% Asian). Baseline pain measures, analgesic responses, and psychological variables are presented in Table 1. As reported previously, significant sex differences in baseline heat pain and pressure pain responses emerged (p's < .05), and there were no sex differences in ischemic pain responses (p's > .10). Also, as reported
Discussion
This study examined psychological predictors of baseline pain and analgesic responses to pentazocine among women and men. An interesting pattern of associations between psychological factors and baseline pain perception emerged. Specifically, while negative affect and catastrophizing were similarly associated with pain perception among women and men, positive affect was associated with lower pain sensitivity only among men. Regarding analgesic responses, catastrophizing and negative affect
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Malcom Randall VA Medical Center, Gainesville, FL, USA. This work was supported by National Institutes of Health Grants NS41670 and General Clinical Research Center Grant RR00082.
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2015, Seminars in Arthritis and RheumatismCitation Excerpt :Several studies have associated elevated catastrophizing with a greater need for opioid analgesics to control pain [19–21]. For example, a study of intravenous pentazocine (an opioid analgesic) in healthy adults revealed that increased indices of catastrophizing were associated with less subsequent analgesic benefit from pentazocine [21]. Indirect evidence that catastrophizing interferes with effective functioning of the endogenous opioid system can also be derived from a psychophysical study in which high catastrophizing healthy participants demonstrated less effective functioning of endogenous pain-inhibitory systems measured using a counter-irritation paradigm [22].