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Pain processing is altered in Native Americans
S48
Abstracts
The Journal of Pain
E10 Endogenous Pain Modulation (288) Emotional modulation of pain and the nociceptive flexion reflex across the menstrual cycle in women with and without premenstrual dysphoric disorder Y Guereca, E Bartley, S Martin, S Palit, K Kerr, E Terry, B Kuhn, J DelVentura, and J Rhudy; The University of Tulsa, Tulsa, OK Premenstrual dysphoric disorder (PMDD) is associated with a disruption of mood and pain processing; specifically, women with PMDD appear to be hyperalgesic. At this time, it is unclear whether this hyperalgesia is due to abnormities in emotional modulation of pain. The present study examined emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological correlate of spinal nociception) in women with PMDD (n=9) and healthy controls (HC, n=14) during the mid-follicular, ovulatory, and late-luteal phases. To do so, participants viewed erotica, neutral, and mutilation pictures in pseudorandom order. During 50% of pictures, suprathreshold electric stimulations were delivered to the sural nerve at the ankle (balanced across content). Electrocutaneous pain ratings and NFR magnitudes were recorded in response to each stimulus and averaged by picture content and menstrual phase. Menstrual phases were verified using daily diaries and luteinizing hormone tests, and order of testing was counterbalanced across participants. A linear mixed model ANOVA was used to analyze pain outcomes by diagnosis (PMDD vs. HC), menstrual phase (mid-follicular, ovulatory, late-luteal), and picture content (erotica, neutral, mutilation). Results indicated that pictures evoked the intended reactions, with mutilation pictures increasing displeasure and arousal, and erotic pictures increasing pleasure and arousal. However, PMDD rated erotic pictures as more pleasurable and more arousing than HC (ps<.05). Despite these differences in the subjective appraisal of pictures, NFR and pain were inhibited in both groups during erotic pictures, relative to neutral and mutilation pictures (ps<.05). Emotional modulation of pain and NFR were not influenced by menstrual phase, but electrocutaneous pain ratings were generally higher during the mid-follicular phase, relative to ovulatory and late-luteal phases. These results suggest that PMDD is not associated with abnormalities in emotional modulation of pain and NFR, nor does emotional modulation vary across the menstrual cycle. Implications are discussed.
(290) Conditioned pain modulation of pain and the nociceptive flexion reflex across the menstrual cycle in women with and without premenstrual dysphoric disorder J DelVentura, E Bartley, S Palit, S Martin, B Kuhn, E Terry, K Kerr, and J Rhudy; The University of Tulsa, Tulsa, OK Premenstrual dysphoric disorder (PMDD) is characterized by severe affective and pain-related symptoms during the late-luteal phase of the menstrual cycle. Furthermore, women with PMDD appear to have a disruption of pain processing, in that they evidence hyperalgesia in response to painful stimuli. At this time, it is unclear whether this hyperalgesia is due to a deficiency in descending inhibitory mechanisms and whether these mechanisms are influenced by menstrual phase. The present study examined conditioned pain modulation (CPM; i.e., pain inhibiting pain) of experimentally-induced pain and the nociceptive flexion reflex (NFR, a physiological correlate of spinal nociception) in healthy controls (HC, n=14) and women with PMDD (n=12) during the mid-follicular, ovulatory, and late-luteal phases. Phase testing order was counterbalanced and menstrual phase was verified using daily diaries and luteinizing hormone surge tests. To assess CPM, participants received painful electric stimulations (the test stimuli) before (baseline), during, and after (post) painful forearm ischemia (the conditioning stimulus). To elicit forearm ischemia, a blood pressure cuff was inflated on the upper arm for two minutes. Participants rated the electric test stimuli using a scale ranging from 0 (no sensation) to 100 (maximum tolerable) and NFR magnitudes were recorded in response to each stimulus. A linear mixed model ANOVA was used to assess CPM by diagnosis (PMDD vs. HC), menstrual phase (mid-follicular, ovulatory, late-luteal), and CPM Phase (baseline, ischemia, post-ischemia). Results indicated that NFR was inhibited in both groups during ischemia, relative to baseline and post-ischemia phases. Also, both groups demonstrated CPM-inhibition of electrocutaneous pain during ischemia, but the inhibition persisted during the post-ischemia phase only in PMDD. Menstrual phase did not influence inhibition of NFR or pain in either group. These results suggest that PMDD is not associated with a deficit of CPMinhibition and that CPM-inhibition does not vary across the menstrual cycle.
(289) Central autonomic circuits regulate lumbar muscles in spinally transected mice: a retrograde transsynaptic tracing study
(291) Pain processing is altered in Native Americans
H Xiang, D Ye, and R Li; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Pain problems are more prevalent in Native Americans than any other group in the U.S.; however, little is known about pain processing in this group. In fact, there are currently no studies of pain processing in Native Americans using well-controlled experimental pain stimuli. The present study was designed to examine pain processing in healthy Native Americans (n=19) relative to healthy, white, non-Hispanic controls (n=20). Pain processing was assessed from electric pain threshold/tolerance, ischemia pain threshold/tolerance, nociceptive flexion reflex (NFR; a physiological measure of spinal nociception) threshold, pain ratings of suprathreshold electric stimuli, and temporal summation of pain and NFR. All procedures were IRB approved. Compared to white controls, Native Americans had a higher electric pain threshold (p=.02), ischemia pain threshold (p=.03) and tolerance (p=.03), and lower ratings of suprathreshold electric stimuli (p=.02). There were no group differences in electric pain tolerance or NFR threshold (ps>.50). Further, Native Americans had overall lower ratings of electric stimuli during temporal summation testing (p=.02), but there were no group differences in pain summation (p=.82). Interestingly though, temporal summation of NFR was reduced in Native Americans (p=.001). Taken together, these findings suggest that Native Americans have altered pain processing, with a tendency to show hypoalgesia on subjective measures of pain. Reduced temporal summation of NFR suggests that the hypoalgesia may result from reduced hyperexcitability of spinal dorsal horn neurons, perhaps due to chronic activation of descending inhibitory processes. These differences in pain processing might put Native Americans at risk for future pain problems if over-activation of inhibitory processes eventually depletes this valuable resource.
Persistent low back pain following spine surgery, the failed back surgery syndrome (FBSS), had developed to a clinical problem. Muscle inflammation or injury clearly causes primary hyperalgesia and secondary hyperalgesia. The CNS descending pathways that coordinate autonomic circuits regulating lumbar muscles are not adequately understood. Here we used both pseudorabies virus (PRV)-614 retrograde transsynaptic tracing and spinally transected method in 33 C57BL/6J mice to map the polysynaptic pathways between lumbar muscle and CNS. Tissues were processed for dual-label immunocytochemical detection between PRV-614 and tryptophan hydroxylase (TPH) or tyrosine hydroxylase (TH)-expressing neurons in CNS. In intact mice, PRV-614 was transported to the intermediolateral column (IML) and ventral horn (VH) of spinal cord, with subsequent transport to many brain regions, including the medullary raphe nuclei, rostral ventrolateral medulla (RVLM), A5 cell group regions (A5), locus coeruleus (LC), the medullary and pontine reticular formation nucleus (MRN and PRN), paraventricular nucleus of the hypothalamus (PVN), and other central sites. In five brain regions including RVLM, Lateral paragigantocellular reticular nucleus (LPGi), A5, LC, and PVN, dual-labeling immunocytochemistry showed coexpression of PRV-614/TPH and PRV-614/TH immunoreactive (IR) neurons involved in these regulatory circuits. Our results reveal a hierarchical organization of central autonomic circuits controlling the lumbar muscles, thus providing neuroanatomical substrates for the central catecholaminergic and serotonergic system to regulate the lumbar muscles.
S Palit, K Kerr, B Kuhn, E Terry, J DelVentura, E Bartley, J Shadlow, and J Rhudy; The University of Tulsa, Tulsa, OK
Abstracts
The Journal of Pain
E10 Endogenous Pain Modulation (288) Emotional modulation of pain and the nociceptive flexion reflex across the menstrual cycle in women with and without premenstrual dysphoric disorder Y Guereca, E Bartley, S Martin, S Palit, K Kerr, E Terry, B Kuhn, J DelVentura, and J Rhudy; The University of Tulsa, Tulsa, OK Premenstrual dysphoric disorder (PMDD) is associated with a disruption of mood and pain processing; specifically, women with PMDD appear to be hyperalgesic. At this time, it is unclear whether this hyperalgesia is due to abnormities in emotional modulation of pain. The present study examined emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological correlate of spinal nociception) in women with PMDD (n=9) and healthy controls (HC, n=14) during the mid-follicular, ovulatory, and late-luteal phases. To do so, participants viewed erotica, neutral, and mutilation pictures in pseudorandom order. During 50% of pictures, suprathreshold electric stimulations were delivered to the sural nerve at the ankle (balanced across content). Electrocutaneous pain ratings and NFR magnitudes were recorded in response to each stimulus and averaged by picture content and menstrual phase. Menstrual phases were verified using daily diaries and luteinizing hormone tests, and order of testing was counterbalanced across participants. A linear mixed model ANOVA was used to analyze pain outcomes by diagnosis (PMDD vs. HC), menstrual phase (mid-follicular, ovulatory, late-luteal), and picture content (erotica, neutral, mutilation). Results indicated that pictures evoked the intended reactions, with mutilation pictures increasing displeasure and arousal, and erotic pictures increasing pleasure and arousal. However, PMDD rated erotic pictures as more pleasurable and more arousing than HC (ps<.05). Despite these differences in the subjective appraisal of pictures, NFR and pain were inhibited in both groups during erotic pictures, relative to neutral and mutilation pictures (ps<.05). Emotional modulation of pain and NFR were not influenced by menstrual phase, but electrocutaneous pain ratings were generally higher during the mid-follicular phase, relative to ovulatory and late-luteal phases. These results suggest that PMDD is not associated with abnormalities in emotional modulation of pain and NFR, nor does emotional modulation vary across the menstrual cycle. Implications are discussed.
(290) Conditioned pain modulation of pain and the nociceptive flexion reflex across the menstrual cycle in women with and without premenstrual dysphoric disorder J DelVentura, E Bartley, S Palit, S Martin, B Kuhn, E Terry, K Kerr, and J Rhudy; The University of Tulsa, Tulsa, OK Premenstrual dysphoric disorder (PMDD) is characterized by severe affective and pain-related symptoms during the late-luteal phase of the menstrual cycle. Furthermore, women with PMDD appear to have a disruption of pain processing, in that they evidence hyperalgesia in response to painful stimuli. At this time, it is unclear whether this hyperalgesia is due to a deficiency in descending inhibitory mechanisms and whether these mechanisms are influenced by menstrual phase. The present study examined conditioned pain modulation (CPM; i.e., pain inhibiting pain) of experimentally-induced pain and the nociceptive flexion reflex (NFR, a physiological correlate of spinal nociception) in healthy controls (HC, n=14) and women with PMDD (n=12) during the mid-follicular, ovulatory, and late-luteal phases. Phase testing order was counterbalanced and menstrual phase was verified using daily diaries and luteinizing hormone surge tests. To assess CPM, participants received painful electric stimulations (the test stimuli) before (baseline), during, and after (post) painful forearm ischemia (the conditioning stimulus). To elicit forearm ischemia, a blood pressure cuff was inflated on the upper arm for two minutes. Participants rated the electric test stimuli using a scale ranging from 0 (no sensation) to 100 (maximum tolerable) and NFR magnitudes were recorded in response to each stimulus. A linear mixed model ANOVA was used to assess CPM by diagnosis (PMDD vs. HC), menstrual phase (mid-follicular, ovulatory, late-luteal), and CPM Phase (baseline, ischemia, post-ischemia). Results indicated that NFR was inhibited in both groups during ischemia, relative to baseline and post-ischemia phases. Also, both groups demonstrated CPM-inhibition of electrocutaneous pain during ischemia, but the inhibition persisted during the post-ischemia phase only in PMDD. Menstrual phase did not influence inhibition of NFR or pain in either group. These results suggest that PMDD is not associated with a deficit of CPMinhibition and that CPM-inhibition does not vary across the menstrual cycle.
(289) Central autonomic circuits regulate lumbar muscles in spinally transected mice: a retrograde transsynaptic tracing study
(291) Pain processing is altered in Native Americans
H Xiang, D Ye, and R Li; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Pain problems are more prevalent in Native Americans than any other group in the U.S.; however, little is known about pain processing in this group. In fact, there are currently no studies of pain processing in Native Americans using well-controlled experimental pain stimuli. The present study was designed to examine pain processing in healthy Native Americans (n=19) relative to healthy, white, non-Hispanic controls (n=20). Pain processing was assessed from electric pain threshold/tolerance, ischemia pain threshold/tolerance, nociceptive flexion reflex (NFR; a physiological measure of spinal nociception) threshold, pain ratings of suprathreshold electric stimuli, and temporal summation of pain and NFR. All procedures were IRB approved. Compared to white controls, Native Americans had a higher electric pain threshold (p=.02), ischemia pain threshold (p=.03) and tolerance (p=.03), and lower ratings of suprathreshold electric stimuli (p=.02). There were no group differences in electric pain tolerance or NFR threshold (ps>.50). Further, Native Americans had overall lower ratings of electric stimuli during temporal summation testing (p=.02), but there were no group differences in pain summation (p=.82). Interestingly though, temporal summation of NFR was reduced in Native Americans (p=.001). Taken together, these findings suggest that Native Americans have altered pain processing, with a tendency to show hypoalgesia on subjective measures of pain. Reduced temporal summation of NFR suggests that the hypoalgesia may result from reduced hyperexcitability of spinal dorsal horn neurons, perhaps due to chronic activation of descending inhibitory processes. These differences in pain processing might put Native Americans at risk for future pain problems if over-activation of inhibitory processes eventually depletes this valuable resource.
Persistent low back pain following spine surgery, the failed back surgery syndrome (FBSS), had developed to a clinical problem. Muscle inflammation or injury clearly causes primary hyperalgesia and secondary hyperalgesia. The CNS descending pathways that coordinate autonomic circuits regulating lumbar muscles are not adequately understood. Here we used both pseudorabies virus (PRV)-614 retrograde transsynaptic tracing and spinally transected method in 33 C57BL/6J mice to map the polysynaptic pathways between lumbar muscle and CNS. Tissues were processed for dual-label immunocytochemical detection between PRV-614 and tryptophan hydroxylase (TPH) or tyrosine hydroxylase (TH)-expressing neurons in CNS. In intact mice, PRV-614 was transported to the intermediolateral column (IML) and ventral horn (VH) of spinal cord, with subsequent transport to many brain regions, including the medullary raphe nuclei, rostral ventrolateral medulla (RVLM), A5 cell group regions (A5), locus coeruleus (LC), the medullary and pontine reticular formation nucleus (MRN and PRN), paraventricular nucleus of the hypothalamus (PVN), and other central sites. In five brain regions including RVLM, Lateral paragigantocellular reticular nucleus (LPGi), A5, LC, and PVN, dual-labeling immunocytochemistry showed coexpression of PRV-614/TPH and PRV-614/TH immunoreactive (IR) neurons involved in these regulatory circuits. Our results reveal a hierarchical organization of central autonomic circuits controlling the lumbar muscles, thus providing neuroanatomical substrates for the central catecholaminergic and serotonergic system to regulate the lumbar muscles.
S Palit, K Kerr, B Kuhn, E Terry, J DelVentura, E Bartley, J Shadlow, and J Rhudy; The University of Tulsa, Tulsa, OK