Acute Pain Sensitivity Research Articles

Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament

While a variety of cultural, psychological and physiological factors contribute to variability in both clinical and experimental contexts, the role of genetic factors in human pain sensitivity is increasingly recognized as an important element. This study was performed to evaluate genetic influences on variability in human pain sensitivity associated with gender, ethnicity and temperament. Pain sensitivity in response to experimental painful thermal and cold stimuli was measured with visual analogue scale ratings and temperament dimensions of personality were evaluated. Loci in the vanilloid receptor subtype 1 gene (TRPV1), δ opioid receptor subtype 1 gene (OPRD1) and catechol O-methyltransferase gene (COMT) were genotyped using 5′ nuclease assays. A total of 500 normal participants (306 females and 194 males) were evaluated. The sample composition was 62.0% European American, 17.4% African American, 9.0% Asian American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage. Female European Americans with the TRPV1 Val585 Val allele and males with low harm avoidance showed longer cold withdrawal times based on the classification and regression tree (CART) analysis. CART identified gender, an OPRD1 polymorphism and temperament dimensions of personality as the primary determinants of heat pain sensitivity at 49 °C. Our observations demonstrate that gender, ethnicity and temperament contribute to individual variation in thermal and cold pain sensitivity by interactions with TRPV1 and OPRD1 single nucleotide polymorphisms.

Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament

While a variety of cultural, psychological and physiological factors contribute to variability in both clinical and experimental contexts, the role of genetic factors in human pain sensitivity is increasingly recognized as an important element. This study was performed to evaluate genetic influences on variability in human pain sensitivity associated with gender, ethnicity and temperament. Pain sensitivity in response to experimental painful thermal and cold stimuli was measured with visual analogue scale ratings and temperament dimensions of personality were evaluated. Loci in the vanilloid receptor subtype 1 gene ( TRPV1), δ opioid receptor subtype 1 gene ( OPRD1) and catechol O-methyltransferase gene ( COMT) were genotyped using 5′ nuclease assays. A total of 500 normal participants (306 females and 194 males) were evaluated. The sample composition was 62.0% European American, 17.4% African American, 9.0% Asian American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage. Female European Americans with the TRPV1 Val 585 Val allele and males with low harm avoidance showed longer cold withdrawal times based on the classification and regression tree (CART) analysis. CART identified gender, an OPRD1 polymorphism and temperament dimensions of personality as the primary determinants of heat pain sensitivity at 49 °C. Our observations demonstrate that gender, ethnicity and temperament contribute to individual variation in thermal and cold pain sensitivity by interactions with TRPV1 and OPRD1 single nucleotide polymorphisms.

Antinociceptive activity of Sempervivum tectorum L. extract in rats.

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract.

The association between anger expression and chronic pain intensity: evidence for partial mediation by endogenous opioid dysfunction

Recent work suggests that an expressive anger management style (anger-out) is associated with elevated acute pain sensitivity due to endogenous opioid antinociceptive dysfunction. We tested the hypothesis that this opioid dysfunction mediates the previously reported positive association between anger-out and chronic pain intensity. To assess endogenous opioid antinociception in the laboratory, 71 subjects with chronic low back pain received opioid blockade (8 mg naloxone i.v.) or placebo in counterbalanced order in separate sessions. During each, subjects participated in a 1-min finger pressure pain task followed by an ischemic forearm pain task, providing acute pain ratings on the McGill Pain Questionnaire–Short Form (MPQ) immediately following each task. Subjects also completed a 7-day chronic pain diary based on the MPQ between laboratory sessions. To index opioid antinociceptive function, blockade effects were derived, subtracting placebo from blockade condition pain ratings. Greater anger-out was associated with both smaller blockade effects (suggesting impaired opioid antinociception) and greater chronic pain intensity, and blockade effects were inversely associated with chronic pain intensity. Sequential hierarchical regressions suggested that opioid dysfunction partially mediates the positive association between anger-out and total MPQ chronic pain intensity. Inclusion of blockade effects in the first step of the regression resulted in a decrease from 7 to 3% in chronic pain variance accounted for by anger-out. Opioid dysfunction did not mediate the positive association between anger-in and chronic pain. These results provide preliminary support for the hypothesis that the positive association between anger expression and chronic pain intensity is mediated by opioid antinociceptive system dysfunction.

Emotion induction moderates effects of anger management style on acute pain sensitivity

Anger management style (AMS) is related to both acute and chronic pain intensity. Recent work suggests that an anger expressive AMS in particular may influence acute pain, and that this effect may be most pronounced during anger provocation. The present study examined whether AMS was related to subsequent pain sensitivity without regard to prior emotion induction, only when a strong negative emotion was evoked, or only when anger was provoked. Sixty-four healthy normals partook in semi-structured interviews in which they recalled and verbally described an event in which either anger, sadness, or joy was elicited. They then underwent a cold pressor pain task. Results of hierarchical multiple regressions showed that an anger expressive AMS was related positively to pain threshold only for participants in the anger-recall condition, and that this effect was largely accounted for by their low SBP reactivity during emotion induction. An anger suppressive AMS was related positively to increases in self-reported pain severity, irrespective of emotion-induction condition, and this effect was not accounted for by reactivity in any cardiovascular index. Results extend those of previous studies by illuminating the potential importance of behavioral anger expression for individuals prone to express anger in modulating their reactivity and pain sensitivity. Findings suggest that the detrimental effects of an anger expressive style on pain sensitivity may be ameliorated under conditions in which behavioral anger expression occurs. Results are discussed in terms of recent work suggesting that an expressive AMS is associated with endogenous opioid dysfunction in the absence of behavioral anger expression.

Theoretical review: altered pain regulatory systems in chronic pain

This review synthesizes the existing literature regarding the relationship between resting blood pressure and pain sensitivity, and the literature indicating possible endogenous opioid dysfunction in chronic pain. Adaptive interactions between the cardiovascular and pain regulatory systems occur in healthy individuals, with greater blood pressure associated with decreased acute pain sensitivity. Endogenous opioids appear necessary for full expression of this relationship. There is ample evidence indicating diminished endogenous opioid CSF/plasma levels in chronic pain patients, yet little is known about the functional effects of these opioid changes. A theoretical model is proposed based upon the literature reviewed suggesting progressive dysfunction in endogenous opioid systems with increasing chronic pain duration. This dysfunction is hypothesized to result in dysregulation of normally adaptive relationships between the cardiovascular and pain regulatory systems, resulting in increased chronic pain intensity and increased acute pain sensitivity among chronic pain patients. Preliminary data are consistent with the hypothesis of progressive opioid changes resulting in dysfunctional alterations in the adaptive blood pressure–pain relationship. Clinical implications of this theory are discussed.

Evidence for a role of endogenous cannabinoids in the modulation of acute and tonic pain sensitivity

The competitive CB1 receptor antagonist SR141716A was used to test the hypothesis that endogenous cannabinoids modulate tonic pain sensitivity. Pretreatment with the antagonist significantly enhanced the response to a chemical nociceptive stimulus in the formalin test. Postreatment with the antagonist 5 min following the induction of tonic pain produced hyperalgesia during the tonic phase only. These findings suggest that endogenous cannabinoids serve naturally to modulate the maintenance of pain following repeated noxious stimulation.

Procedures which increase acute pain sensitivity also increase autotomy

Rats typically display self-mutilation (autotomy) of a paw that has been denervated by transection of the sciatic and saphenous nerves. The cause of autotomy, however, is not known. It may be due to hyperesthesia (comparable to that seen in humans after peripheral nerve injury) or anesthesia (as an attempt to shed an insensate appendage). The present study tested the assumption that if autotomy is produced by pain, then procedures that normally augment the expression of pain should enhance autotomy after transection of peripheral nerves. Groups of rats were subjected to procedures known to produce an increase in pain sensitivity: (i) prior heat injury of either the ipsilateral or contralateral paw; (ii) systemic injection of noradrenaline and the monoamine oxidase inhibitor, pargyline; and (iii) intrathecal administration of substance P. The results showed that each of these procedures produced an increase in the level of autotomy. These results strongly suggest that autotomy is due to a sensory phenomenon which, in terms of human experience, would be described as pain or dysesthesia.