Group differences in pain modulation: Pain-free women compared to pain-free men and to women with TMD

Dental Research Center, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599-7175, USA.
Pain (Impact Factor: 5.21). 05/2002; 96(3):227-37. DOI: 10.1016/S0304-3959(01)00451-1
Source: PubMed


Previously reported differences in sensitivity to experimental pain stimuli between the sexes, as well as between temporomandibular disorder (TMD) patients and healthy control subjects, may be attributable in part to group differences in two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous opioid system. Twenty-two pain-free (PF) men, 20 PF women and 20 women with TMD underwent two testing sessions in which heat pain and ischemic arm pain threshold and tolerance were measured during both sessions, but followed relaxation during one session and laboratory stress tasks during the other. Blood pressure (BP) and plasma -endorphin (E) concentration were measured during a baseline rest and during the stress or relaxation periods. PF men's threshold and tolerance for heat pain, but not for ischemic pain, exceeded that of PF women's during both sessions. PF women and TMD women did not differ in sensitivity to either pain modality; however, significantly lower ischemic pain threshold (IPTh) was linked to oral contraceptive use in PF women but not TMD patients. In the men alone, higher baseline systolic BP (SBP) was correlated with higher heat pain threshold on both days and heat pain tolerance on the stress day. Conversely, in TMD women, higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on both days; BP and pain sensitivity were not related in PF women. In men, but not in PF or TMD women, stress systolic and diastolic BP were positively correlated with heat pain threshold and tolerance and higher diastolic reactivity to stress were correlated with higher heat pain and IPTh and tolerance. On the stress day, higher baseline E level was strongly associated with higher IPTol in PF women but marginally associated with lower IPTol in TMD women. Thus, it appears that a BP-related analgesic mechanism (probably baroreceptor-mediated) predominates in PF men, while an endogenous opioid mechanism predominates in PF women. Stress enhances the expression of these central mechanisms. Female TMDs appear unable to effectively engage normal pain-inhibitory systems; opioid receptor desensitization and/or downregulation are probably implicated, because TMDs' production of E appears normal.

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    • "In conjunction with alterations in the ascending pathways, evidence suggests that the descending pain modulatory pathway in TMD (and other musculoskeletal/inflammatory pain conditions) is also affected (Bragdon et al., 2002; Kashima et al., 1999; King et al., 2009, Linnman et al., 2012). Interestingly, the most significant area of MD difference in TMD subjects was located in the PAG, a region shown to display anatomical changes in other chronic pain conditions (DaSilva et al., 2007; Rocca et al., 2006; Seminowicz et al., 2010). "
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    ABSTRACT: Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 05/2015; 117. DOI:10.1016/j.neuroimage.2015.05.014 · 6.36 Impact Factor
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    • "Temporomandibular joint disorders (TMD) represent a family of conditions associated with pain in the temporomandibular joint (TMJ) and masticatory muscles and shares several features with other idiopathic pain conditions such as fibromyalgia and irritable bowel syndrome (Yunus, 2007; Maixner, 2009; Bereiter and Okamoto, 2011). Notably, pain expression often correlates poorly with signs of peripheral tissue damage (Ohrbach and Dworkin, 1998) and TMD patients often display evidence of altered endogenous pain controls (Bragdon et al., 2002; King et al., 2009; Oono et al., 2014). These features suggest a central nervous system (CNS) dysfunction in persistent TMD pain (Sarlani and Greenspan, 2005; Fernandez-de-las-Penas et al., 2009; Pfau et al., 2009; Slade et al., 2014). "
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    ABSTRACT: Repeated forced swim (FS) conditioning enhances nociceptive responses to temporomandibular joint (TMJ) stimulation in male and female rats. The basis for FS-induced TMJ hyperalgesia remains unclear. To test the hypothesis that serotonin 3 receptor (5HT3R) mechanisms contribute to enhanced TMJ nociception after FS, ovariectomized female rats were treated with estradiol and subjected to FS for three days. On day 4, rats were anesthetized with isoflurane and TMJ-responsive neurons were recorded from superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical (Vc/C1-2) region and electromyographic (EMG) activity was recorded from the masseter muscle. Only Vc/C1-2 neurons activated by intra-TMJ injections of ATP were included for further analysis. Although neurons in both superficial and deep laminae were activated by ATP, only neurons in deep laminae displayed enhanced responses after FS. Local application of the 5HT3R antagonist, ondansetron (OND), at the Vc/C1-2 region reduced the ATP-evoked responses of neurons in superficial and deep laminae and reduced the EMG response in both sham and FS rats. OND also decreased the spontaneous firing rate of neurons in deep laminae and reduced the high threshold convergent cutaneous receptive field area of neurons in superficial and deep laminae in both sham and FS rats. These results revealed that central application of a 5HT3R antagonist, had widespread effects on the properties of TMJ-responsive neurons at the Vc/C1-2 region and on jaw muscle reflexes under sham and FS conditions. It is concluded that 5HT3R does not play a unique role in mediating stress-induced hyperalgesia related to TMJ nociception. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 04/2015; 299. DOI:10.1016/j.neuroscience.2015.04.037 · 3.36 Impact Factor
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    • "Less efficient DNIC was reported in various populations of idiopathic pain disorders, such as tempomandibular disorder [3] [4] [5] [6]; irritable bowel syndrome [3] [7] [8]; fibromyalgia [9] [10] [11] [12] [13]; and tensiontype headache [14]. Furthermore, less efficient DNIC was found to be associated with a higher self-report of pain history among healthy subjects [15]. "
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    ABSTRACT: Background and purposeConditioned pain modulation (CPM) is a testing paradigm representing features of diffuse noxious inhibitory control. There is large diversity in the paradigms applied to induce CPM, and the consistency in CPM responses assessed by different paradigms is largely unknown. We aimed to characterize and explore the associations between the CPM responses assessed by different paradigms in the same cohort.Methods Thirty-three healthy middle-aged subjects underwent six CPM paradigms. The ‘test-stimuli’, consisted of thermal and mechanical modalities, using pain thresholds, suprathreshold pain and temporal summation types of measurements. The ‘conditioning-stimulus’ consisted of a contact heat stimulus applied to the thener of the left hand for 60 s at an intensity of 46.5 °C.ResultsLarge variability was observed among the responses to the different CPM paradigms. Surprisingly, no correlations were found between the various CPM responses.Conclusions The variability in the CPM responses may suggest that the capacity of pain modulation is a multifaceted trait, whose expression varies with the application of different CPM paradigms.ImplicationsConsidering that CPM responses may represent different processes when assessed by different paradigms, we encourage the use of more than one CPM paradigm.
    Scandinavian Journal of Pain 01/2013; 4(1):10–14. DOI:10.1016/j.sjpain.2012.08.001
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