Differences In Pain Sensitivity Research Articles

Removal of the Submaxillary Salivary Glands and Infection with the Trematode Schistosoma mansoni Alters Exploratory Behavior and Pain Thresholds in Female Mice

Fiore, M., R. Moroni and L. Aloe. Removal of the submaxillary salivary glands and infection with the trematode Schistosoma mansoni alters exploratory behavior and pain thresholds in female mice. Physiol Behav 62(2) 399–406, 1997.—In this study, CD-1 female mice, deprived of the submaxillary salivary glands, were infected with S. mansoni and their behavior was observed 15 weeks after infection, when the eggs of the parasite are present in the brain. Sialectomized infected mice showed changes in exploratory activity, sniffing, and wall-rearing in the open-field and in the black/white box, but no differences in pain sensitivity were observed on the hot plate. The present results suggest that the modifications in the behavior of sialectomized infected mice might be associated with the inability of the animals to cope with the aversive effects of the infection and, most probably, with modifications in the levels of polypeptides released into the bloodstream by the salivary glands, affecting the NGF-responsive cells of the nervous, endocrine, and immune systems.

Pain from rectal distension in women with irritable bowel syndrome: relationship to sexual abuse.

The aims of this study were to determine whether increased pain sensitivity in patients with irritable bowel is due to physiological differences in perceptual sensitivity or psychological influences on perception, and whether prior sexual abuse accounts for increased pain sensitivity. Seventeen sexually abused and 15 nonabused women with irritable bowel were compared to 13 sexually abused and 14 nonabused women without irritable bowel. Among the nonabused subjects, the volume of rectal distension that produced moderate pain was lower in IBS patients than in controls, replicating earlier studies, but these thresholds were correlated with psychological measures of anxiety and somatization. The ability to discriminate between painful distensions (perceptual sensitivity) was not different between groups. Sexual abuse was not associated with lower pain thresholds. Thus, differences in pain sensitivity appear to be due to psychological influences on perception, but a history of sexual abuse does not contribute significantly to this pain sensitivity.

Pain sensitivity and stability of physical aggression in boys.

It is unclear whether stably aggressive boys would be characterized by high or low pain sensitivity. Adolescent boys in whom physical aggression, executive functioning, anxiety, and family adversity had been assessed longitudinally formed three groups who differed in stability of physical aggression: stable, unstable, and non-aggressive. Stable aggressives were the least pain sensitive, whereas unstable aggressives were the most pain sensitive. While at low levels of executive functioning pain sensitivity could not be distinguished between the aggressive groups, at high levels unstable aggressives reported even more pain, whereas stable aggressives reported even less pain. Variations in anxiety were associated strongly with pain sensitivity in unstable aggressives. High pain ratings were found in boys who had a moderate level of family adversity, and low pain ratings in boys with low or high adversity. The differences in pain sensitivity between the groups may be motivationally important to the frequency and type of aggression.

The influence of resting blood pressure and gender on pain responses.

Recent research suggests that resting blood pressure is inversely related to pain sensitivity, even among normotensives; however, most of these studies have included only male participants. To determine whether this hypoalgesic effect of blood pressure was also present in females, we investigated thermal and ischemic pain responses in a group of age-matched, normotensive females and males as a function of resting blood pressure. Thermal pain threshold and tolerance were determined, and a cross-modality thermal magnitude matching procedure was conducted, after which ischemic pain threshold and tolerance were determined using the submaximal effort tourniquet procedure. Systolic pressure, diastolic pressure, and heart rate were obtained using an automated blood pressure monitor with a pneumatic cuff positioned around the left ankle. Females provided higher normalized thermal magnitude estimates and a shorter time to ischemic pain tolerance, but no gender differences emerged on other pain measures. Systolic, diastolic, and mean arterial pressures were significantly correlated with thermal and ischemic pain responses among males but not females, with higher blood pressure being associated with lower pain sensitivity. After adjusting for resting blood pressure, the gender difference in normalized magnitude estimates was only marginally significant, and the gender difference in ischemic pain tolerance became nonsignificant. These findings are consistent with previous research indicating an inverse relationship between blood pressure and pain sensitivity. Additionally, the findings also suggest that blood pressure may partially moderate gender differences in pain sensitivity. Potential mechanisms and clinical implications of the current findings are discussed.

Gender differences in pain: Epidemiologic perspectives

I n their Focus article, Drs. Fillingim and Maixner have reviewed data on gender differences in responsiveness to experimental noxious stimuli, interpreted those data as indicating that women are more sensitive to noxious stimuli than men, and proposed a model of how a range of biological and psychological factors might contribute to these gender-associated differences in pain sensitivity. The model is intriguing and is well grounded in the animal literature on sex differences in pain transmission and pain modulation systems. However, because the authors' stated motivation for assessing gender-related differences in pain responsiveness is that certain pain conditions (e.g., migraine headache, fibromyalgia, temporomandibular disorder pain) are more prevalent in women than in men, and that persons with these predominantly female pain conditions exhibit enhanced sensitivity to laboratory pain procedures, additional perspectives from clinical and epidemiologic pain research may be relevant. Specifically, this commentary will introduce an epidemiologic approach to the issue of gender differences in pain that may be useful for exploring alternative interpretations of the data presented and identifying strengths and weaknesses of the model proposed. Epidemiology is the study of the distribution and determinants of diseases or conditions in populations. '° The science of epidemiology is grounded in three important perspectives: the population perspective, the ecological perspective, and the developmental perspective. Elsewhere, we have presented an extensive discussion of the application of these perspectives to the study of pain: This article focuses 'more specifically on what these three perspectives have to offer in terms of

Gender differences in the responses to noxious stimuli

Many clinical pain conditions, including migraine, fibromyalgia, and temporomandibular disorders, occur more frequently among females than males. Greater pain sensitivity among females has been considered as one possible explanation for these differences. Despite considerable clinical and experimental research on the topic, no consensus has emerged on the existence or nature of gender differences in response to noxious stimuli. In this Focus article the authors take the position that females exhibit greater sensitivity to noxious stimuli than males. In support of this position, they review the experimental literature on gender and pain responses. Then, they present and discuss a schematic model of several systems involved in the transmission and modulation of nociceptive information, which may contribute to gender-associated differences in pain sensitivity. Finally, the authors highlight several issues to be addressed by future research in this area.

Diet and estrous cycle influence pain sensitivity in rats

Effects of estrous cycle and acute and chronic access to palatable fluids on tail-flick latency and opiate-induced analgesia were assessed in 124 female Long Evans rats. Following three consistent cycles, rats were water deprived for 8 h and then given ad lib access to 20 ml of either water, a 32% sucrose solution, or corn oil for 5 h. Nociceptive testing was conducted immediately preceding and 30, 60, and 90 min following an SC injection of morphine sulfate (7.5 mg/kg). Diestrus rats had prolonged premorphine tail-flick latencies compared to rats in proestrus. Rats that consumed corn oil had longer tail-flick latencies preceding and 30 min following morphine injections than rats that drank water or the sucrose solution. Rats were tested after they had ad lib access to the same fluid for 3 weeks. No estrous cycle differences were noted following chronic consumption. Rats with chronic access to sucrose showed increased baseline pain sensitivity and increased morphine-induced analgesia at 30, 60, and 90 min postinjection. These data support the notion that palatable fluid consumption attenuates estrous cycle-dependent differences in pain sensitivity.

Pain sensitivity and pain reactivity of pericranial muscles in migraine and tension-type headache.

We investigated whether experimentally determined, suprathreshold pain sensitivity of pericranial musculature in patients with tension-type headache differs from that of migraine patients or from that of healthy subjects. Furthermore, we looked to see whether differences could be found in the effects of experimental pain induction on EMG activity of pericranial musculature and whether subgroups could be discovered with higher and lower pericranial pain sensitivity within the three diagnostic groups in terms of neurophysiological, psychological and clinical variables. In 20 patients with tension-type headache, 23 patients with migraine without aura, and 29 healthy individuals experimental pain was induced in the temporal muscle by mechanical pressure; pain sensitivity in the entire metrically subdivided suprathreshold pain sensitivity range was measured. Surface EMG activity of pericranial muscles was determined before, during and after experimental pain induction. In addition, headache characteristics as well as personality and mood states were determined and recorded in a standardized fashion. There were no significant differences in pain sensitivity of pericranial musculature between the three groups. Patients with tension-type headache showed significantly higher EMG scores during suprathreshold pain stimulation than did migraine patients. EMG scores of healthy subjects fell between these two groups. With respect to pericranial tenderness significant differences in clinical, neurophysiological and psychological variables were found only between subgroups within the group of patients with tension-type headache. The results indicate that significant differences in the examined groups are found not in pain perception but in the processing or reaction to experimental headache stimuli. In patients with tension-type headache subgroups evolve based on pericranial pain sensitivity with quantitatively and/or qualitatively impaired reactions; for this reason diagnostic grouping according to the IHS classification seems to be pathophysiologically relevant. The intraindividual phasic comparison of pain reactions appears to be more important than the absolute interindividual tonic comparison.

Pain sensitivity in offspring of hypertensives at rest and during baroreflex stimulation

Healthy males with a parental history of hypertension (PH+) showed reduced pain sensitivity to a constrictive thigh-cuff pressure stimulus as compared to individuals without a parental history of hypertension. The protocol included eight trials in which a thigh-cuff was inflated until the subject reported the stimulus to be "painful." The PH+ group exhibited significantly lower pain sensitivity as indicated by (1) higher levels of constrictive pressure when pain was first reported and (2) lower subjective pain ratings at maximum constrictive pressure. To assess the role of baroreflex stimulation on pain sensitivity in these groups, four trials were administered concurrently with external carotid pressure stimulation. There were no significant differences in pain sensitivity in each group as a function of baroreflex stimulation. The results suggest that the hypoalgesia observed in hypertensives may predate the development of sustained elevations in blood pressure.

A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls

Differences in pain sensitivity between chronic pain patients and healthy controls have been reported. Seltzer and Seltzer extended this line of research in studying the sensitivity to non-painful stimuli. They reported that the 2-point discrimination threshold of chronic pain patients was higher than that of control subjects. However, the study of Seltzer and Seltzer suffered from several methodological shortcomings. Therefore, in the present study we tried to replicate the findings in a group of chronic low back pain patients using a design that was believed to be methodologically stronger. Replication failed: no evidence was found for the hypothesis that chronic pain patients are less sensitive to non-painful stimuli. Further studies on various defined types of acute and chronic pain patients are required.

Circadian Variation of Pain Sensitivity in Pericranial Musculature

This study investigated whether pain sensitivity of the pericranial musculature remains constant over the course of the day. Changes in the entire, uniformly metrically divided suprathreshold sensitivity range were measured. In 24 healthy volunteer subjects, pain was induced experimentally at 0200, 0600, 1000, 1400, 1800, and 2200 hours in the pericranial musculature. Blood circulation in both superficial temporal and occipital arteries was reduced by applying a cuff to the head pumping up to 200 mmHg during rhythmic chewing on a spring, thereby producing a continuously increasing bilateral, dull, frontal headache. The subjects rated the intensity continuously using a category sub-dividing procedure ranging from pain threshold to pain tolerance limit. At low levels of headache intensity there were no significant diurnal differences in pain sensitivity. Sensitivity to very intense headache, however, varied significantly over the course of the day: sensitivity was greatest at 0200 hours; it decreased at a constant rate until 1400 hours, and increased again continuously until 2200 hours (p less than or equal to .05). Also the findings showed significant effects of sex on the pain sensitivity of pericranial musculature for all pain intensities: women are approx. twice as sensitive as men (p less than or equal to 0.05). These results suggest that not only sex, but also time of day, must be taken into consideration in the clinical determination of pain sensitivity of pericranial musculature in the course of headache diagnostics.

Individual differences in pain sensitivity and the analgesic effect of morphine in noninbred mice

individual differences in pain sensitivity and the analgesic effect of morphine in noninbred mice

Normal pain sensitivity in patients with panic disorder

The pain sensitivity of 18 patients with panic disorder and age- and sex-matched controls was assessed by signal detection analysis. The authors failed to demonstrate any difference in pain sensitivity between the two groups. The relationship between state anxiety, as assessed by the Spielberger scale, and pain in panic patients tended to be in the opposite direction from that in normals.

Genetic differences in avoidance behavior: Cardiovascular activity, pain sensitivity and stress-induced analgesia

Four experiments are reported which examine cardiovascular activity, pain sensitivity and stress-induced analgesia in rats selectively bred for differences in shuttlebox avoidance behavior. The results of Experiments 1 and 2 indicate that the two genetic lines differ in basal pain sensitivity, as measured by the hot-plate test. This difference in pain sensitivity appears not to be mediated by endogenous opioids, because it was not altered by pretreatment with a large dose of naloxone. In Experiments 1, 3 and 4 tail-flick tests of basal pain sensitivity failed to reveal line differences. Basal and stress levels of cardiovascular activity also showed no differences between the lines. In Experiment 3, LA but not HA animals showed profound stress-induced analgesia which was not blocked by a large dose of naltrexone. In Experiment 4, both LA and HA animals showed stress-induced analgesia, perhaps because the procedure of this experiment permitted conditioning mechanisms to contribute to the analgesia. Differential genetic selection for avoidance behavior also selected for differential pain sensitivity and some forms of non-opioid stress-induced analgesia but without concomitant selection for differential cardiovascular activity.

Pain sensitivity and coping strategies among dysmenorrheic women: Much ado about nothing

Samples of spasmodic, congestive and combined dysmenorrheic women and non-dysmenorrheic women were subjected to an ischemic pain procedure to measure their pain threshold, pain tolerance and self-reported pain. Cognitive and behavioral strategies that subjects had spontaneously used during the pain procedure were later assessed. A classification system was derived for categorizing subjects' responses to the interview and questionnaire used in this assessment. Contrary to previous claims that dysmenorrheic women may be hypersensitive to pain, no differences in pain sensitivity were discovered among the four groups of subjects. A few differences in cognitive and behavioral strategies did emerge, but these were of insufficient magnitude to contend that dysmenorrheic women are disadvantaged in their strategies for coping with pain.

VARIATIONS IN THE PAIN REACTIONS OF HOSPITAL PATIENTS

The tenability of an exclusively “medical model” explanation of pain is called into question. The pain experience is a “mediated” one; the brain regulates the pain experience through its electrochemical activities and attentiveness to pain stimuli. The latter is largely the result of conditioning processes, many of which are related to ethno-cultural attitudes. Zborowski found differential pain responses among American patients of Yankee, Italian and Jewish ancestry. Sternbach and Tursky discovered differing reactions to electric shock among American housewives of Yankee, Irish, Italian and Jewish ancestry. Chapman and Jones studied the pain responses of American negroes, and Caucasian Americans of Northern European, Italian, and Russian Jewish ancestry and concluded that differences in pain sensitivity and reaction exist which are related to ethno-cultural origins. These ethno-cultural differences are discussed and some speculative explanations are offered. The implications of these observations for hospital staff, particularly nurses, are examined and some specific remedies for related problems are presented.

Opiate pharmacology and individual differences. I. Psychophysical pain measurements.

A new electric stimulation pain assessment technique using the Tursky electrode and a non-parametric analysis of subjects ratings was found sensitive to aspirin, morphine and opiate antagonists in a series of double-blind cross-over trials in normal adults. Stable individual differences in pain sensitivity (off medication) were maintained on two testing sessions 7 months apart. Older individuals were less pain sensitive than younger individuals. Men were more insensitive than women under age 30. Together, these results suggest the empiric usefulness of this pain measurement technique.

The neural substrate of the startle response

Fifteen rats were exposed to various intensities of startle-eliciting auditory stimulation and footshock, and measures of response probability and amplitude were obtained. Subjects then received (1) lesions directed at the nucleus reticularis gigantocellularis (RGI), (2) lesions directed at the nucleus reticularis pontis caudalis (RPC) or (3) no lesions. After surgery, all subjects were tested for the same measures of startle responsiveness as had been collected in the pre-operative series. In addition, sensitivity to heat-induced pain and running wheel activity were also evaluated. Subjects with lesions of RPC showed a significant decrease in both the probability and amplitude of response to footshock as well as to acoustic signals. Subjects in the other two groups did not show significant decreases in responsiveness. No difference in pain sensitivity was found between groups. Subjects with lesions of RPC, however, were more (rather than less) active than the unoperated subjects. These data support the hypothesis that the mammalian startle response is elaborated through the nucleus reticularis pontis caudalis.

Naloxone alters pain perception and somatosensory evoked potentials in normal subjects : M.S. Buchsbaum, G.C. Davis and W.E. Bunney, Nature (Lond.), 270 (1977) 620–622

THE discovery of opiate-like peptides (endorphins) in brain, blood and cerebrospinal fluid1–4 raises questions as to the physiological role of these substances. Given the prominent analgesic effects of opiates, the regulation of pain perception is a candidate for endorphin action. Endorphins microinjected into the periacqueductal grey matter of rats induce analgesia which is reversed by naloxone, a pure narcotic antagonist5. If endorphins play an active part in the regulation of pain, then naloxone administered to man should alter pain appreciation. Naloxone has not been shown to have analgesic, respiratory, euphoric, pupillary or electroencephalogram (EEG) effects in man6. Studies in rats7,8 and one early study in man9 have suggested slight hyperalgesic effects with naloxone. El-Sobky et al.10 failed to demonstrate naloxone effects on electric shock pain judgments in five subjects. In the experiments reported here, subjects were divided into pain sensitive and pain insensitive subgroups. The insensitive subjects found shocks significantly more painful after naloxone administration while the sensitive group experienced them as less painful. Evoked potentials showed similar significant group differences. These results suggest that individual differences in pain sensitivity may relate to differences in an endorphin system.

Naloxone alters pain perception and somatosensory evoked potentials in normal subjects

THE discovery of opiate-like peptides (endorphins) in brain, blood and cerebrospinal fluid1–4 raises questions as to the physiological role of these substances. Given the prominent analgesic effects of opiates, the regulation of pain perception is a candidate for endorphin action. Endorphins microinjected into the periacqueductal grey matter of rats induce analgesia which is reversed by naloxone, a pure narcotic antagonist5. If endorphins play an active part in the regulation of pain, then naloxone administered to man should alter pain appreciation. Naloxone has not been shown to have analgesic, respiratory, euphoric, pupillary or electroencephalogram (EEG) effects in man6. Studies in rats7,8 and one early study in man9 have suggested slight hyperalgesic effects with naloxone. El-Sobky et al.10 failed to demonstrate naloxone effects on electric shock pain judgments in five subjects. In the experiments reported here, subjects were divided into pain sensitive and pain insensitive subgroups. The insensitive subjects found shocks significantly more painful after naloxone administration while the sensitive group experienced them as less painful. Evoked potentials showed similar significant group differences. These results suggest that individual differences in pain sensitivity may relate to differences in an endorphin system.