Search PubMed⌕ Search

Biomedical subjects

William Maixner

Publications and source records attributed to William Maixner.

At least 19 recordsLinked to original sources
PubMed2006

Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors.

Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint Disorder (TMJD) and are associated with heightened experimental pain sensitivity [Diatchenko, L, Slade, GD, Nackley, AG, Bhalang, K, Sigurdsson, A, Belfer, I, et al., Genetic basis for individual variations in pain perception and the development of a chronic pain condition, Hum Mol Genet 2005;14:135-43.]. Variants associated with heightened pain sensitivity produce lower COMT activity. Here we report the mechanisms underlying COMT-dependent pain sensitivity. To characterize the means whereby elevated catecholamine levels, resulting from reduced COMT activity, modulate heightened pain sensitivity, we administered a COMT inhibitor to rats and measured behavioral responsiveness to mechanical and thermal stimuli. We show that depressed COMT activity results in enhanced mechanical and thermal pain sensitivity. This phenomenon is completely blocked by the nonselective beta-adrenergic antagonist propranolol or by the combined administration of selective beta(2)- and beta(3)-adrenergic antagonists, while administration of beta(1)-adrenergic, alpha-adrenergic, or dopaminergic receptor antagonists fail to alter COMT-dependent pain sensitivity. These data provide the first direct evidence that low COMT activity leads to increased pain sensitivity via a beta(2/3)-adrenergic mechanism. These findings are of considerable clinical importance, suggesting that pain conditions resulting from low COMT activity and/or elevated catecholamine levels can be treated with pharmacological agents that block both beta(2)- and beta(3)-adrenergic receptors.

Animals↗
PubMed2006

GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.

We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolin-stimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits.

Adult↗
PubMed2006

Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.

Activation of the beta(2) adrenergic receptor (beta(2)AR) located on macrophages has been reported to possess anti-inflammatory properties, inhibiting nuclear factor kappaB (NF-kappaB) activation and cytokine production induced by pro-inflammatory stimuli. Here, we show that activation of the beta(2)AR in the absence of pro-inflammatory stimuli produced up to an 80- and 8-fold increase in IL-1beta and IL-6 transcripts, respectively, in the RAW 264.7 murine macrophage cell line. This increase in mRNA expression was accompanied by a significant increase in IL-1beta and IL-6 protein production. Pre-treatment of RAW cells with pharmacological inhibitors of protein kinase A (PKA) or NF-kappaB pathway failed to block this cytokine increase. Instead, the beta(2)AR-mediated increase in cytokines required activation of both the B-raf-ERK1/2 and p38 pathways. Treatment of RAW cells with the exchange protein directly activated by cAMP (EPAC) agonist also resulted in the up-regulation of IL-1beta and IL-6 transcripts. Examination of the main transcription factors downstream of the ERK1/2 and p38 signaling revealed that beta(2)AR activation resulted in the stimulation of CRE-, but not C/EBPbeta-, ETS-, or NF-kappaB-dependent transcription. Western blot analysis further showed that among the transcription factors which recognize the CRE-binding site, ATF-1 and ATF-2 but not CREB proteins were phosphorylated in an ERK1/2- and p38-dependent manner. Collectively, these results demonstrate that beta(2)ARs possess pro-inflammatory properties and that their activation leads to IL-1beta and IL-6 production through ERK1/2- and p38-dependent activation of ATF-1 and ATF-2 transcription factors.

Activating Transcription Factors↗
PubMed2006

Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.

Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences in pain sensitivity. A single nucleotide polymorphism (SNP) in codon 158 (val(158)met), which affects COMT protein stability, has been associated with the human experience of pain. We recently demonstrated that three common COMT haplotypes, which affect the efficiency of COMT translation, are strongly associated with a global measure of pain sensitivity derived from individuals' responses to noxious thermal, ischemic, and pressure stimuli. Specific haplotypes were associated with low (LPS), average (APS), or high (HPS) pain sensitivity. Although these haplotypes included the val(158)met SNP, a significant association with val(158)met variants was not observed. In the present study, we examined the association between COMT genotype and specific pain-evoking stimuli. Threshold and tolerance to thermal, ischemic, and mechanical stimuli, as well as temporal summation to heat pain, were determined. LPS/LPS homozygotes had the least, APS/APS homozygotes had average, and APS/HPS heterozygotes had the greatest pain responsiveness. Associations were strongest for measures of thermal pain. However, the rate of temporal summation of heat pain did not differ between haplotype combinations. In contrast, the val(158)met genotype was associated with the rate of temporal summation of heat pain, but not with the other pain measures. This suggests that the val(158)met SNP plays a primary role in variation in temporal summation of pain, but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity. Here, we propose a mechanism whereby these two genetic polymorphisms differentially affect pain perception.

Adolescent↗
PubMed2006

Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder.

Adrenergic receptor beta(2) (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. These genetic variants should also interact with environmental factors such as physical or emotional stress to produce a phenotype vulnerable to pathological states. In this study, we determined whether common genetic variants of ADRB2 contribute to the development of a common chronic pain condition that is associated with increased levels of psychological distress and low blood pressure, factors which are strongly influenced by the adrenergic system. We genotyped 202 female subjects and examined the relationships between three major ADRB2 haplotypes and psychological factors, resting blood pressure, and the risk of developing a chronic musculoskeletal pain condition-Temporomandibular Joint Disorder (TMD). We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist-induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options.

Adolescent↗
PubMed2006

Stress-induced muscle and cutaneous hyperalgesia: differential effect of milnacipran.

We previously demonstrated that repeated swim stress produces long-term cutaneous hyperalgesia in rats. We have now determined the effect of stress upon muscle nociception and the anti-nociceptive efficacy of the norepinephrine-serotonin reuptake inhibitor, milnacipran (MIL) in this model. Rats were subjected to either 10-20 min daily sessions of forced swimming (FS) for 3 days, or sham swimming (SS) or control (CT). Maximal forelimb grip strength and hot plate response latencies were estimated before and after the conditioning to assess muscle and thermal nociception, respectively. MIL (1-30 mg/kg/i.p.) or vehicle was started 7 days before the conditioning protocol. There were significant reductions in maximal grip strength and hot plate latencies only in FS/vehicle rats. Subsequent carrageenan administration (2 mg/75 microl each triceps) diminished grip strength in all groups 24 h later, with grip strength lower in FS/vehicle and SS/vehicle rats than in CT/vehicle rats. Treatment with MIL before the stress prevented the reduction in grip strength in all groups but it was ineffective in preventing FS-induced reductions in hot plate response latencies. Thus, repeated stress produces muscle hyperalgesia that can be pharmacologically dissociated from cutaneous hyperalgesia, suggesting that different mechanisms may underlie these two phenomena.

Analysis of Variance↗
PubMed2006

Effects of carrageenan and morphine on acute inflammation and pain in Lewis and Fischer rats.

The present study used inbred, histocompatible Fischer 344 (FIS) and Lewis (LEW) rats to begin to explore the role of the hypothalamic-pituitary-adrenal (HPA) axis in the immune processes and pain behavior associated with the carrageenan model of acute hindpaw inflammation. Because the HPA axis contributes in part to morphine's analgesic and immunomodulatory properties, the present study also assessed the effects of morphine in carrageenan-inflamed LEW and FIS rats. The results showed that carrageenan-induced hindpaw swelling and pain behavior were greater in FIS than in LEW rats. The enhanced hindpaw swelling in FIS rats correlated with an increase in myeloperoxidase (MPO; a measure of neutrophils) in the inflamed hindpaw. FIS rats showed lower circulating levels of TNFalpha, higher IL-6 levels, and similar IL-1beta and nitric oxide levels, when compared to LEW rats. Morphine produced a significant decrease in carrageenan-induced hindpaw swelling and MPO in both strains, but morphine did not significantly alter circulating cytokine/mediator levels. Morphine's analgesic effects were greater in the inflamed than the noninflamed hindpaw, and they did not correlate with morphine's anti-inflammatory effects. In fact, low doses of morphine produced a mechanical allodynia and hyperalgesia in the noninflamed hindpaw of FIS, but not LEW, rats. These results suggest a positive relationship between HPA axis activity and acute inflammation and inflammatory pain. In contrast, little evidence is provided for HPA axis involvement in morphine's anti-inflammatory or analgesic effects.

Acute Disease↗
PubMed2006

A conceptual model for the pathophysiology of vulvar vestibulitis syndrome.

UNLABELLED: Vulvar vestibulitis syndrome (vestibulitis), the most common type of chronic vulvovaginal pain, impairs the psychologic, physical, and reproductive health of approximately 10% of women at some point in their lives. Research on the pathophysiology of vestibulitis suggests abnormalities in 3 interdependent systems: vestibular mucosa, pelvic floor muscles, and central nervous system pain regulatory pathways. To date, causes and relative contributions of these abnormalities to the development and maintenance of vestibulitis remain poorly understood. Research consistently supports the conceptualization of vestibulitis as a chronic pain disorder-akin to fibromyalgia, irritable bowel disorder, and temporomandibular disorder (TMD)-that is far more complex than vestibular hypersensitivity alone. Nevertheless, the clinical diagnosis of vestibulitis continues to rely on subjective report of pain during intercourse and vestibular sensitivity on clinical examination after exclusion of other gynecologic disorders. We propose that current diagnostic criteria, which are based on highly subjective patient and clinician measures, are not sufficient to describe and properly classify the heterogeneous clinical presentations of this disorder. To inform clinical care or research, we must be able to objectively characterize women with vestibulitis. This narrative review critically appraises current conceptualization of vestibulitis and presents a context for studying vestibulitis as a chronic pain disorder, emphasizing the need for objective assessment of clinical features. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that vulvar vestibulitis is common; recall that the disorder has three major pathophysiological pathways and that understanding of these pathways is important in selecting treatment options, and explain that the clinician must attempt to properly classify the clinical presentations of the disorder.

Female↗
PubMed2005

Role of mu-opioid and NMDA receptors in the development and maintenance of repeated swim stress-induced thermal hyperalgesia.

Repeated exposure to swimming stress induces a long-lasting hyperalgesia in the rat by mechanisms to be elucidated. Since opioid and glutamate neurotransmitter systems modulate pain, we now evaluated the effect of pharmacological blockade of opioid and glutamate receptors subtypes on forced swimming stress-induced hyperalgesia. Male rats were daily subjected to 10-20 min of forced or sham swimming for 3 days and thermal nociception was estimated twice, before each behavioral conditioning and 24 h after the last, using hot plate test. Selective opioid and NMDA receptor antagonists were administered i.p. either before each conditioning session or before the second nociception assessment. Unlike sham swimming rats, forced swimming rats showed significant reductions in hot plate response latencies (hyperalgesia) after the last swimming session, as compared to pre-stress values. Rats treated with the opioid receptor antagonists naloxone (0.1 mg/kg, non-subtype-selective) and naloxonazine (5 mg/kg, mu(1)-subtype-selective), before each forced swimming, did not become hyperalgesic, whereas those treated before the second post-stress assessment of nociception developed hyperalgesia. Naltrindole (0.5 mg/kg, delta-subtype-selective) and nor-binaltorphimine (0.5mg/kg, kappa-subtype-selective) were inactive in both administration schedules. The efficacy of morphine (3-7.5 mg/kg) to produce analgesia in forced swimming rats was lower than in sham swimming rats. Rats treated with the NMDA antagonist ketamine (5 mg/kg) before the forced swimming or the second post-stress assessment of nociception did not have hyperalgesia. Thus, swim stress-induced hyperalgesia might be initiated by the repeated stimulation of mu-opioid and NMDA receptors but maintained only by the activity of NMDA receptors.

Analysis of Variance↗
PubMed2005

Basal and carrageenan-induced pain behavior in Sprague-Dawley, Lewis and Fischer rats.

Individual differences in pain sensitivity are believed to reflect the interplay of many factors, including genetics. Inbred rat strains can be used to study the impact of genetic factors on pain sensitivity. Inbred Lewis (LEW) and Fischer 344 (FIS) rat strains display profound and contrasting alterations in neuroendocrine, immunological and behavioral responses to stressors. Because of the established interactions between stressors, the neuroendocrine system, the immune system and pain processing pathways, we hypothesized that LEW and FIS rats would differ in their pain sensitivity. Pain sensitivity was assessed using several behavioral pain assays in untreated and carrageenan-inflamed LEW and FIS rats, and in the outbred Sprague-Dawley (SD) rat. The results showed that at baseline, FIS rats were the most sensitive to mechanical stimulation (the von Frey monofilament test) and the least sensitive to noxious heat pain (the Hargreaves radiant heat test). After intraplantar administration of carrageenan, LEW rats showed the least, and FIS rats showed the greatest, thermal hyperalgesia and mechanical allodynia/hyperalgesia. Hindlimb muscle grip force and tail-flick latencies did not differ across the three strains, either before or after carrageenan. These results demonstrate differences in basal and carrageenan-induced pain sensitivity in LEW, FIS and SD rats, which extend earlier findings that genetic factors modulate both basal and inflammatory pain. The results further demonstrate that basal pain sensitivity can be predictive of inflammatory pain sensitivity, with the direction of the effect dependent upon the pain measure.

Analysis of Variance↗
PubMed2005

Comparison of Fos expression within the ferret's spinal trigeminal nuclear complex evoked by electrical or noxious-thermal pulpal stimulation.

UNLABELLED: Fos-like immunoreactivity (Fos-LI) was used as a marker of trigeminal neurons that responded to tooth pulp stimulation. The activation of intradental afferents was produced by electrical stimulation of the ferret's intact canine tooth, whereas natural stimuli that activate predominantly Adelta (5 mol/L CaCl2 applied to dentin) or C fibers (slow heating of the intact tooth) were used to stimulate the 2 populations of afferents selectively. Electrical stimulation evoked Fos-LI in ipsilateral dorsomedial of the trigeminal subnucleus caudalis (Vc), dorsomedial and ventrolateral of the transition zone between subnucleus interpolaris and caudalis (Vi/Vc), and the the paratrigeminal nucleus (Pa5). Osmotic stimulation evoked Fos-LI in the ipsilateral dorsomedial Vc and Vi/Vc. The spatial distribution of Fos labeling after heat stimulation was dependent on the duration and location of the stimulus application. Repeated heating of the maxillary canine for 30 minutes evoked labeling bilaterally in ventrolateral Vi/Vc. Stimulation of the maxillary and mandibular canines with heat pulses for 1 hour produced labeling in the ipsilateral dorsomedial Vc, dorsomedial Vi/Vc, and the Pa5. None of the stimulating procedures did evoke Fos expression in regions rostral to Vi/Vc. Regardless of the pulpal stimulation procedures, a similar number of Fos-positive neurons was found in the nucleus of solitary tract and the ventrolateral medulla. Although Fos expression does not reveal all neurons that respond to noxious pulpal stimulation, it marks many neuronal regions that contain neurons that respond to pulpal stimulation and injury. Our results suggest that a population of neurons in Vc and Vi/Vc contribute to painful sensations originating from the dentition. PERSPECTIVE: We demonstrated that the trigeminal nucleus caudalis and the transitional zone between trigeminal interpolaris and caudalis mediate painful sensation in the dental pulp. Both trigeminal regions might be therapeutic targets for dental pain in the future.

Afferent Pathways↗
PubMed2005

Associations among four modalities of experimental pain in women.

UNLABELLED: The aim of this study was to investigate the associations among 4 measures of pain induction procedures in 244 healthy women. The procedures were (1) pressure pain threshold assessed over the temporalis muscles, masseter muscles, temporomandibular joints, and the wrists; (2) C fiber-mediated heat pain threshold/tolerance assessed on the skin over the forearm, cheek, and dorsal aspect of the foot; (3) temporal summation of C fiber-mediated heat pain; and (4) ischemic pain threshold/tolerance. Strong associations among pressure pain thresholds at the 4 sites examined (rho = 0.7 to 0.8, P values < or = .001) and among heat pain threshold/tolerance values at the 3 sites examined (rho = 0.6 to 0.9, P values < or = .001) were observed. Pressure pain threshold was moderately correlated with each of the heat pain threshold/tolerance values (rho = 0.2 to 0.4, P values < or = .001). Ischemic pain threshold/tolerance was moderately associated with each of the pressure and heat pain measures (rho = 0.2 to 0.3, P values < or = .05 to .001). Derived measures of the temporal summation of heat pain did not correlate strongly with threshold or tolerance measures of pressure, ischemic, or heat pain. We concluded (1) that for a specific pain modality, the correlation between threshold and tolerance values across anatomic sites is high, and (2) that measures of pressure, ischemic, and thermal pain threshold/tolerance are significantly correlated, although the strength of these associations is moderate. These findings demonstrate that a battery of pain-assessing procedures is required to determine an individual's pain sensitivity profile or phenotype. PERSPECTIVE: By investigating the relationship between pain sensitivity produced by different forms of stimuli, this study demonstrates that a battery of tests should be used to assess an individual's pain sensitivity and one should be careful in making inferences about an individual's sensitivity to pain by using only one pain modality.

Adolescent↗
PubMed2005

Cigarette smoking, stress-induced analgesia and pain perception in men and women.

This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers (P<0.05) when pain testing followed rest. Male smokers had greater threshold and tolerance to cold pressor pain than male nonsmokers (P<0.05) after both rest and stress. Only women showed evidence for SIA, since women nonsmokers demonstrated greater ischemic pain threshold and tolerance following mental stress versus rest (P<0.05), and all women reported lower thermal heat pain unpleasantness after stress versus rest (P=0.05). Only nonsmokers showed expected inverse relationships between sympathetic and hypothalamic-pituitary-adrenal (HPA) axis reactivity measures and sensitivity to pain. Smokers showed evidence for blunted HPA-axis function at rest and stress. These results indicate that analgesia related to both being a smoker and stress is influenced by gender and pain modality. The reduced pain perception in smokers and absence of relationships between endogenous pain regulatory mechanisms and pain sensitivity may reflect a maladaptive response to chronic smoking.

Adrenocorticotropic Hormone↗
PubMed2004

Genetic basis for individual variations in pain perception and the development of a chronic pain condition.

Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.

Adolescent↗
PubMed2004

Suramin inhibits spinal cord microglia activation and long-term hyperalgesia induced by formalin injection.

UNLABELLED: Previous studies in our laboratory have shown that long-term (a period of weeks) increases in pain-related behavior were correlated with the activation of spinal microglia after subcutaneous injection of formalin into the dorsal surface of 1 hind paw. The present study examined whether intrathecal delivery of suramin (a P2 receptor antagonist) blocks microglia activation and long-term hyperalgesia induced by formalin injection. Suramin was administered by using an osmotic pump attached to an intrathecal catheter. Suramin delivery (1.25 microg/kg/h) began 1 day before the formalin injection and lasted for 4 days. Rats were observed by using a modified hot plate test before and at different times after formalin injection. The spinal cord was surveyed for changes in microglia labeling as shown by OX-42 staining at different times after formalin injection. Suramin decreased both the hyperalgesic sensitivity to the thermal stimuli and microglial activation induced by formalin injection as compared to the saline-treated group. This suggests that adenosine triphosphate is one potential mediator that activates spinal cord microglia and enhances pain-related behavior in the formalin model. PERSPECTIVE: This report suggests that blocking specific spinal P2 receptors might decrease the central enhancement of pain caused by peripheral injury and inflammation. One mechanism might be by blocking the activation of spinal microglia. Thus, P2 antagonists might have therapeutic usefulness in certain pain conditions.

Adenosine Triphosphate↗
PubMed2004

Catastrophizing predicts changes in thermal pain responses after resolution of acute dental pain.

UNLABELLED: Substantial research suggests that coping strategies, especially catastrophizing, play an important role in shaping adjustment to chronic pain. Although laboratory and clinical studies both suggest that catastrophizing enhances pain, the interaction of catastrophizing and clinical pain on pain sensitivity has received little attention. The present study evaluated the extent to which catastrophizing influenced laboratory thermal pain responses during and after the resolution of acute dental pain. Thermal pain threshold and tolerance, as well as self-reported catastrophizing, were determined in 46 dental patients (15 men and 31 women) experiencing pain as a result of acute pulpitis. All subjects participated in 2 experimental sessions; the first took place immediately before endodontic treatment for relief of pulpal pain, and the second session occurred when patients were pain free, approximately 1 to 2 weeks later. Thermal pain thresholds increased on resolution of acute dental pain, whereas levels of catastrophizing did not change from pretreatment to post-treatment. Catastrophizing was unrelated to thermal pain responses in the presence of acute dental pain (ie, during the first session). Once patients were pain free, catastrophizing showed significant inverse associations with measures of thermal pain threshold and tolerance. In addition, catastrophizing was a robust predictor of changes in thermal pain responses across sessions, with higher baseline catastrophizing predicting reductions or relatively smaller increases in pain threshold and tolerance after successful treatment of acute pain. These data suggest that catastrophizing is prospectively associated with enhanced sensitivity to and reduced tolerance for thermal pain. The use of catastrophizing as a coping strategy might interfere with the resolution of sensitization after cessation of an acutely painful condition, or it might be associated with magnified experimental pain responses across time. PERSPECTIVE: The findings of the present study suggest that, in some instances, different ethnic groups and genders may use the same descriptors to report different levels of pain. In the context of clinical pain assessment, it may be important to consider the possibility that descriptions of painful sensations reflect, in part, demographic characteristics.

Adaptation, Psychological↗