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Pain perception and response: central nervous system mechanisms.

Although several decades of studies have detailed peripheral and ascending nociceptive pathways to the thalamus and cerebral cortex, pain is a symptom that has remained difficult to characterize anatomically and physiologically. Positron emission tomography (PET) and functional magnetic imaging (fMRI) have recently demonstrated a number of cerebral and brain stem loci responding to cutaneous noxious stimuli. However, intersubject variability, both in the frequency and increased or decreased intensity of the responses, has caused uncertainty as to their significance. Nevertheless, the large number of available imaging studies have shown that many areas with recognized functions are frequently affected by painful stimuli. With this evidence and recent developments in tracing central nervous system connections between areas responding to noxious stimuli, it is possible to identify nociceptive pathways that are within, or contribute to, afferent spino-thalamo-cortical sensory and efferent skeletomotor and autonomic motor systems. In this study it is proposed that cortical and nuclear mechanisms for pain perception and response are hierarchically arranged with the prefrontal cortex at its highest level. Nevertheless, all components make particular contributions without which certain nociceptive failures can occur, as in pathological pain arising in some cases of nervous system injury.

Amygdala↗

The effects of music on pain perception of stroke patients during upper extremity joint exercises.

The purpose of this study was to determine the effects of music therapy on pain perception of stroke patients during upper extremity joint exercises. Ten stroke patients (1 male and 9 females) ranging in age from 61 to 73 participated in the study. Music conditions used in the study consisted of: (a) song, (b) karaoke accompaniment (same music to condition A except singers' voices), and (c) no music. Exercise movements in this study included hand, wrist, and shoulder joints. During the 8-week period music therapy sessions, subjects repeated 3 conditions according to the randomized orders and subjects rated their perceived pain on a scale immediately after each condition. The General Linear Model (GLM) Repeated Measures ANOVA revealed that there were no significant differences in pain rating across the three music conditions. However, positive affects and verbal responses, while performing upper extremity exercises with both music and karaoke accompaniment music, were observed using video observations.

Aged↗

Underlying mechanisms of impaired visceral pain perception in older people.

There is increasing recognition that aging can have a profound effect on the presentation of illness. Older patients with diseases of visceral organs are much more likely than younger adults to present atypically. Examples are the frequent absence of pain in older patients with conditions such as myocardial infarction, peptic ulcer disease, and pneumothorax. Recent developments have helped elucidate the complex processes involved in signaling information from the effects of noxious stimuli on visceral organs, but understanding of why older patients with visceral disease are more likely to present without pain is still rudimentary. Much of the previous experimental evidence on age-related differences relates to somatic rather than visceral sources of pain. As a result, it may not have direct comparability with transmission of information on visceral damage or noxious stimulation. This article reviews the published pathophysiological data on sensory transmission from visceral organs. Where possible, this is correlated with other published clinical studies on age-related differences in visceral pain perception. Areas in which experimental evidence is absent are also highlighted. Finally suggestions are made as to how newer experimental and neuroimaging techniques may help to increase understanding of this complex subject and its resulting clinical applicability.

Aged↗

[Diurnal variation of pain perception and heart rate in the human tourniquet pain model in healthy volunteers].

The diurnal variation of pain threshold was studied in 13 healthy volunteers (age: 21 - 27 ys) using the tourniquet pain model. A tourniquet was inflated above systolic blood pressure for 1 minute and pain scores and heart rate were recorded at 0.5, 1.0, 1.5 and 2.0 minutes. The test was repeated during a study day at 6.00 h, 12.00 h, 18.00 h and 24.00 h. Significant differences of pain scores between clocktimes were found 1 minutes after inflation and after 1.5 minutes with regard to heart rate. Generally, the highest pain scores were found at 24.00 h.

Adult↗

Tonic pain perception in the mouse: differential modulation by three receptor-selective opioid agonists.

The proposition that tonic nociception models are more analogous to clinical pain than traditional acute models prompted our previous development of a modified mouse paw formalin test. To discern possible modulatory roles and site(s) of action of endogenous opioid systems, the receptor-preferring agonists sufentanil (mu), U-50,488H (kappa) and [D-Pen2,5]enkephalin (DPDPE, delta) were evaluated for antinociceptive activity in the formalin paradigm by systemic (except DPDPE), spinal and supraspinal routes. All observations were done under blind conditions. Doses causing overt behaviors that indicated a breach of receptor specificity (during the observation period) were rejected. Higher doses of centrally administered DPDPE (greater than 0.3 micrograms/mouse, intrathecal; greater than 3 micrograms/mouse, intracerebroventricular) induced a behavioral syndrome traditionally associated with mu agonism, and thus were not considered for this study. A50 values from behaviorally acceptable dose ranges for mean percent analgesia (reduction of paw licking compared to controls) were: trans-(+/- )-3,4-dichloro-N-methyl-N-[U-50,488H 2-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate,U-50,488H--3200 nmol/kg, subcutaneous, 1100 nmol/kg, intrathecal and 314 nmol/kg, intracerebroventricular; sufentanil--11.1 nmol/kg, subcutaneous, 8.6 nmol/kg, intrathecal; and DPDPE--inactive. On the basis of our dose-response data, we suggest that, in mice, kappa and mu, but not delta, opioid receptors modulate tonic pain perception at both spinal and supraspinal loci. The results also support inclusion of the modified formalin test in preclinical evaluations of potential kappa agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Serum endothelin levels and pain perception in patients with cardiac syndrome X and in healthy controls.

The possible algogenic effects of elevated serum endothelin levels in cardiac syndrome X were investigated in a case-control study that examined somatic pain perception in the forearm during submaximal effort tourniquet and cold immersion tests. Pain threshold to both ischemic and cold stimulation of the forearm was demonstrated to be significantly lower in patients with syndrome X than in matched healthy controls, and a negative correlation between ischemic pain threshold and endothelin levels was demonstrated.

Aged↗

Coronary vasodilator reserve, pain perception, and sex in patients with syndrome X.

BACKGROUND: It remains unclear whether myocardial ischemia due to coronary microvascular dysfunction is the cause of chest pain in syndrome X (chest pain, ischemic-like stress ECG despite angiographically normal coronary arteries). To assess the function of the coronary microcirculation and its relation to pain perception, we measured myocardial blood flow (MBF) and coronary vasodilator reserve (CVR) in 29 patients with syndrome X and 20 matched normal control subjects. METHODS AND RESULTS: MBF at rest and after intravenous dipyridamole (0.56 mg.kg-1 over 4 minutes) was measured using positron emission tomography with H2(15)O. CVR was calculated as MBFdipyridamole/MBFrest. ECG changes and chest pain after dipyridamole in syndrome X were compared with those in 35 patients with coronary artery disease (CAD). Resting and postdipyridamole MBFs were homogeneous throughout the left ventricle in syndrome X patients and control subjects. MBF was 1.05 (0.25), mean (SD) versus 1.00 (0.22) mL.min-1.g-1 (P = NS) at rest and 2.73 (0.81) versus 3.00 (1.00) mL.min-1.g-1 (P = NS) after dipyridamole in patients and control subjects, respectively. CVRs were 2.66 (0.76) and 3.06 (1.08) (P = NS) and after correction of resting MBF for rate-pressure product were 2.35 (0.83) and 2.34 (0.90) (P = NS) in patients and control subjects, respectively. Female syndrome X patients had higher resting MBF than males, at 1.18 (0.20) versus 0.88 (0.19) mL.min-1.g-1 (P < .001). Chest pain after dipyridamole occurred in syndrome X as frequently as in CAD (21/29 versus 22/35, P = NS). CONCLUSIONS: When patients with syndrome X are compared with control subjects, no differences are found in MBF either at rest or after dipyridamole, despite syndrome X patients experiencing chest pain after dipyridamole to the same extent as patients with CAD. These findings, together with the absence of any relation among MBF, chest pain, and ECG changes under stress, cast further doubt on ischemia as the basis of the chest pain, at least in the majority of syndrome X patients.

Adult↗

Testing different biphasic waveforms and capacitances: effect on atrial defibrillation threshold and pain perception.

OBJECTIVES: The goal of this study was to compare the effect of different tilts and capacitances for biphasic shocks on atrial defibrillation efficacy and pain threshold. BACKGROUND: Although biphasic shocks have been shown to be superior to monophasic shocks, the effect of tilt and capacitance on atrial defibrillation success and pain perception has not been studied in patients. METHODS: Atrial defibrillation threshold (DFT) testing was performed using a right atrial appendage/coronary sinus lead configuration in 38 patients with a history of paroxysmal atrial fibrillation undergoing an invasive electrophysiologic study. Biphasic waveforms with 40%, 50%, 65%, 80%, 30%/50% and 40%/50% were tested randomly in 22 patients (Group 1). In 16 patients (Group 2), a 65% tilt waveform with 50- and 120-microF capacitance was tested. Before sedation, pain sensation was graded by 15 patients in Group 1 after delivery of a 0.5-J shock and by 10 patients in Group 2 after two 1.5-J shocks with 50- and 120-microF capacitance were delivered. RESULTS: The DFT energy for the 50% tilt waveform was significantly lower than the 65%, 80% and 30%/50% tilt waveforms. The 40%/50% tilt waveform provided slightly lower energy requirements than the 50% tilt waveform. Nine patients (60%) described the 0.5-J shock as very painful, and four (26.6%) complained of slight pain. The 50-microF capacitor lowered energy requirements compared with the 120-microF capacitor. Six patients (60%) perceived the 1.5-J 50-microF capacitor shock as more painful, whereas three (30%) perceived both shocks as equally painful. CONCLUSIONS: Biphasic waveforms with 50% tilt in both phases and a smaller tilt in the positive phase than that in the negative phase (40%/50%) provided a decrease in energy requirements at atrial DFT. In addition, stored energy was reduced by biphasic shocks with 50-microF capacitance compared with 120-microF capacitance. Despite the reduction in energy requirements, shocks < 1 J continued to be perceived as painful in the majority of patients.

Aged↗

Spinal cord swelling as a myelographic indicator of prognosis: a retrospective study in dogs with intervertebral disc disease and loss of deep pain perception.

The association of myelographic spinal cord swelling with neurological outcome was examined in 46 dogs with intervertebral disc disease and absence of deep pain perception (DPP). Spinal cord swelling was measured by calculating a ratio of the length of the loss of the myelographic dye column to the length of the second lumbar vertebra (L2). A positive neurological outcome was defined as return of voluntary motor function. A cut-off value for swelling:L2 of 5.0 was established by the creation of a receiver operator characteristic curve. Using a swelling:L2 ratio of 5.0 as a cutoff for indication of neurological recovery yielded a sensitivity of 74% and a specificity of 61%. Overall neurological recovery rate was 43%. Dogs with spinal cord swelling:L2 ratios less than 5.0 had a recovery rate of 61%, whereas dogs with a ratio greater than or equal to 5.0 had a recovery rate of 26%. Evaluation of these data by chi square analysis confirmed that a ratio less than 5.0 was associated with a positive outcome, and a ratio greater than or equal to 5.0 was associated with a negative outcome, (P < .05). Although other factors, such as duration of neurological signs, affect neurological outcome in dogs with no DPP, evaluation of myelographic spinal cord swelling can assist in establishing a prognosis.

Animals↗

Pain perception in idiopathic cervical dystonia (spasmodic torticollis).

Cervical spinal pain is frequently found in conjunction with idiopathic cervical dystonia (ICD), a focal dystonia characterized by sustained deviation of the head. Since the perception of noxious stimuli has never been studied in ICD, we performed a controlled study to obtain more insight into the psychophysics of dystonia-related muscle pain by evaluating pressure-induced pain levels. In nine ICD patients and five gender- and age-matched asymptomatic control subjects, pain-pressure thresholds (PPTs) were determined in the sternocleidomastoid and upper trapezius muscles, both at resting activity and at maximal voluntary contraction (MVC). The masseter muscles served as non-pathological control regions. To determine the accuracy of PPT values, pain intensity and unpleasantness were rated at threshold on 100-mm visual analogue scales. Four replication measurements were obtained. The data were analyzed by multilevel procedures. For all muscles under investigation, average PPTs of the ICD patients were about two times lower than those of the control subjects (P < 0.001-0.0005) and showed a smaller intra-subject variance. Further, average PPTs at MVC were about two times higher than those at resting activity (P < 0.005). These results provide psychophysical evidence to suggest that, at controlled levels of muscle contraction, the threshold of pain perception is decreased in ICD. In addition, ICD patients seem to be better able to establish their own PPTs than control subjects, which might be due to a different setting of the discriminative aspect of pain in ICD. Surprisingly, lower intensity and unpleasantness scores were found in ICD patients with coinciding painful and deviated sides than in ICD patients for whom the painful side was opposite to the deviated one (P < 0.05). This finding might be of clinical importance for defining functional disability and predicting treatment outcome.

Adult↗

Determinants of pain perception in labour among parturients at the University College Hospital, Ibadan.

This cross-sectional study of one thousand parturients aims to evaluate the factors, which are associated with pain perception in labour and to identify women who will benefit most from analgesia in labour. The instrument applied was a structured questionnaire incorporating the Box numerical scale (BNS) for pain assessment. Patients who delivered by elective or emergency caesarean section and women who did not give informed consent were excluded from the study. Spearman's and Pearson's correlational analyses were applied. Pain scores showed significant correlation with age (r=- 0.087, p<0.01), parity (r=- 0.226, p<0.01), gestational age at delivery (r=- 0.074, p<0.05), onset of labour (rho=0.195, p<0.01), mode of delivery (rho=0.160, p<0.01), booking status (rho=- 0.070, p<0.05) and educational status (rho=0.182, p<0.01). Certain groups of patients would benefit from obstetric analgesia. These patients include, nulliparous patients, young patients, patients who have had labour induced, those with preterm deliveries and those with an assisted vaginal delivery especially if they are well educated.

Adult↗

The dimensionality of verbal descriptors in Tursky's pain perception profile.

In the first part of the study 20 subjects (11 headache, 9 normals) free-sorted descriptors from the intensity and affect scales of the Tursky pain perception profile (PPP) into groups on the basis of similar meaning. In part 2 they made similarity ratings of all pairs of words within the intensity and affect scales. In the third part of the study subjects completed a cross-modal matching task to scale the intensity and affect words. Data from the first 2 parts of the study were examined with multidimensional scaling (MDS) and hierarchical cluster analyses. Free-sorting the descriptors did not produce 2 groups corresponding to the intensity and affect descriptors described in the Tursky PPP. The descriptors were arranged in 6 groups described by subjects as reflecting increasing painfulness. An MDS analysis showed that the groups could be located in 2-dimensional space in which the dimensions of intensity and affective distress could be easily discerned. When the descriptors from the intensity and affect scales were rated within each scale, a second MDS analysis showed that, whereas the intensity descriptors could be fitted by a 1-dimensional representation, the affect descriptors required a 3-dimensional model. There was evidence that subjects with extensive pain experience placed greater weight on the second and third affective dimensions compared with relatively pain-free subjects.

Adolescent↗

Pain perception to the cold pressor test during the menstrual cycle in relation to estrogen levels and a comparison with men.

Animal and human research has shown that pain sensitivity changes during the menstrual cycle. This has sometimes been ascribed to hormonal variations. The aim of the present study was to examine how perception of pain, induced by the cold pressor test to the dominant hand, was related to gender and phases of the menstrual cycle. A repeated-measures design was used, where twenty-two female students participated at two different phases of the menstrual cycle (days 2-4 and days 20-24). A control group of nineteen male students participated on two occasions, separated by a three week period. The cycle phase during which each woman began her participation was randomized. Pain was induced using the cold pressor test. Pain threshold was determined as the duration of time between when the subject first reported pain and exposure to the painful stimulus. Pain tolerance was determined as the duration of time until the subject withdraw her/his hand from the test water because the pain was too intensive. The results showed that men tolerated significantly greater pain than women. Women's pain threshold was significantly higher during the second phase of the menstrual cycle. Systolic pressure was higher in men than women, increasing more in men in response to cold pressor testing than women. Further research, including measurements of plasma hormone levels during the menstrual cycle, is needed to clarify the role played by estrogens in pain perception.

Adult↗

Endorphins and pain perception in silent myocardial ischemia.

Evidence suggests that endogenous opioids, particularly the beta-endorphins and met-enkephalins, are closely involved in stress-induced analgesia and nociceptive pain control. Numerous investigations have been conducted to evaluate the role of opioids in silent vs symptomatic myocardial disease. There is good evidence to suggest that patients with asymptomatic ischemia have defective pain perception compared with those with angina; however, the precise role of the endorphin and enkephalin systems in this phenomenon remains to be elucidated. Possible sources for disparate study results include variation in patient populations, insensitive or improperly timed assay techniques, and differences in amount of ischemia.

Angina Pectoris↗

Acupuncture before delivery: effect on pain perception and the need for analgesics.

Pain experience and the amount of analgesics needed during labor were studied in 32 primiparous women who had received repeated treatment with acupuncture (AP) during the month prior to term and in 16 nontreated primiparous women. The women's psychological profiles were evaluated by a psychiatric interview at week 38 of pregnancy. Treatment with AP did not reduce the need for analgesics in labor. During labor, all women experienced successively rising pain irrespective of whether or not they had been treated with AP prior to labor or delivered under local anesthesia. Experience of pain was not reduced in subjective assessments in women treated with AP. There was a strong correlation between assessments of pain made during labor and 6 months after delivery. In the group that did not receive AP, cerebrospinal fluid dynorphin A was significantly lower in parturients who chose epidural anesthesia.

Acupuncture Analgesia↗

Effect of durotomy on functional outcome of dogs with type I thoracolumbar disc extrusion and absent deep pain perception.

Spinal cord durotomy is performed as a diagnostic aid in determining spinal cord structural integrity, and this may be useful as an indicator of prognosis in cases with loss of deep pain perception (DPP). It has been suggested that a durotomy may relieve intramedullary compression but there is some debate about the therapeutic value. The purpose of this study was to compare ambulatory outcome of dogs that had loss of DPP treated with hemilaminectomy with durotomy versus hemilaminectomy without durotomy. Medical records of 81 dogs diagnosed with type I thoracolumbar IVD were reviewed. Dogs were included in the study if DPP was absent upon initial neurological examination and surgical decompression via hemilaminectomy was performed. Of the 81 cases, 48 were included in this study. The number of dogs that recovered ambulatory function were compared between durotomy and non-durotomy groups with a chi-squared test (p < 0.05). No differences were found. The findings of this study suggest that durotomy is useful as a diagnostic modality and that performing a durotomy does not significantly affect post-operative recovery of voluntary motor function.

Animals↗

Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans.

The purpose of the present study was to determine whether gender differences exist in the forebrain cerebral activation patterns of the brain during pain perception. Accordingly, positron emission tomography (PET) with intravenous injection of H2(15)O was used to detect increases in regional cerebral blood flow (rCBF) in normal right-handed male and female subjects as they discriminated differences in the intensity of innocuous and noxious heat stimuli applied to the left forearm. Each subject was instructed in magnitude estimation based on a scale for which 0 indicated 'no heat sensation'; 7, 'just barely painful' and 10, 'just barely tolerable'. Thermal stimuli were 40 degrees C or 50 degrees C heat, applied with a thermode as repetitive 5-s contacts to the volar forearm. Both male and female subjects rated the 40 degrees C stimuli as warm but not painful and the 50 degrees C stimuli as painful but females rated the 50 degrees C stimuli as significantly more intense than did the males (P=0.0052). Both genders showed a bilateral activation of premotor cortex in addition to the activation of a number of contralateral structures, including the posterior insula, anterior cingulate cortex and the cerebellar vermis, during heat pain. However, females had significantly greater activation of the contralateral prefrontal cortex when compared to the males by direct image subtraction. Volume of interest comparison (t-statistic) also suggested greater activation of the contralateral insula and thalamus in the females (P < 0.05). These pain-related differences in brain activation may be attributed to gender, perceived pain intensity, or to both factors.

Adolescent↗