W. Crawford Clark

Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone

&NA; The effects of intense exercise on pain perception, mood, and plasma endocrine levels in man were studied under naloxone and saline conditions. Twelve long‐distance runners (mean weekly mileage = 41.5) were evaluated on thermal, ischemie, and cold presser pain tests and on mood visual analogue scales (VAS). Blood was drawn for determination of plasma levels of &bgr;‐endorphin‐like immunoreactivity (BEir), growth hormone (GH), adrenocorticotrophic hormone (ACTH), and prolactin (PRL). These procedures were undertaken before and after a 6.3 mile run at 85% of maximal aerobic capacity. Subjects participated on two occasions in a double‐blind procedure counterbalanced for drug order: on one day they received 2 i.v. injections of naloxone (0.8 mg in 2 ml vehicle each) at 20 min intervals following the run; on the other day, 2 equal volume injections of normal saline (2 ml). Sensory decision theory analysis of the responses to thermal stimulation showed that discriminability, P(A), was significantly reduced post‐run under the saline condition, a hypoalgesic effect; response bias, B, was unaffected. Ischemie pain reports were significantly reduced post‐run on the saline day, also a hypoalgesic effect. Naloxone reversed the post‐run ischemie but not thermal hypoalgesic effects. Joy, euphoria, cooperation, and conscientiousness VAS ratings were elevated post‐run; naloxone attenuated the elevation in joy and euphoria ratings only. Plasma levels of BEir, ACTH, GH, and PRL were significantly increased post‐run. The results show that long‐distance running produces hypoalgesia and mood elevation in man. The effects of naloxone implicate endogenous opioid neural systems as mechanisms of some but not all of the run‐induced alterations in mood and pain perception.

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

Objective: The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors. Methods: Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion—that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI). Results: IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 (“mild” pain) vs 5.2 (“weak” pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = −0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r = −0.26; p = 0.001) and BSI global score (r = −0.18; p = 0.035). Similar results were seen for the non-painful sensation of urgency. Conclusion: Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.

Antagonism of nitrous oxide analgesia by naloxone in man.

The possible reversal of nitrous oxide analgesia by naloxone was investigated. Two studies were conducted in 21 healthy male subjects, who responded to ischemic pain produced by tourniquet applied to the upper arm for 15 min, while breathing air or nitrous oxide, 33 per cent. Using a double-blind procedure, the subjects received intravenous injections of naloxone and saline solution on different days. In eight subjects, naloxone, 8 mg, administered without nitrous oxide, had no effect on pain report. However, unlike saline solution, naloxone, 8 mg, decreased significantly the analgesia induced by nitrous oxide. In 13 subjects, naloxone, 4 mg, also decreased significantly the effect of nitrous oxide analgesia in comparison with saline solution. Naloxone showed its reversal effect mainly on sensory response ratings obtained during the painful stages of ischemia, between 11 and 15 min. The results suggest that analgesia induced by nitrous oxide may be partly related to the opiate receptor-endorphin system in man.

Effects of cognitive coping skills training on coping strategies and experimental pain sensitivity in African American adults with sickle cell disease.

The present study examined whether training in cognitive coping skills would enhance pain coping strategies and alter pain perception in adults with sickle cell disease (SCD). Sixty-four African Americans with SCD were randomly assigned to either a cognitive coping skills condition (three 45-min sessions in which patients were trained to use 6 cognitive coping strategies) or a disease-education control condition (three 45-min didactic-discussion sessions about SCD). Pain sensitivity to calibrated noxious stimulation was measured at pre- and posttesting, as were cognitive coping strategies, clinical pain, and health behaviors. Results indicated that, compared with the randomly assigned control condition, brief training in cognitive coping skills resulted in increased coping attempts, decreased negative thinking, and lower tendency to report pain during laboratory-induced noxious stimulation.

Pain responsivity in major depression and bipolar disorder

Signal detection theory measures of thermal pain responsivity were examined in patients with major depression and bipolar disorder and in control subjects. Patients with major depression had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but they did not differ from the control subjects in their sensory discrimination of warm thermal stimuli of lower intensity. Patients with bipolar disorder did not differ significantly in sensory discrimination from either the patients with major depression or the control subjects. Patients with major depression had significantly higher (i.e., more stoical) response criteria than the control subjects for the painful thermal stimuli and also for the lower intensity stimuli; patients with bipolar disorder had significantly higher criteria than control subjects for only the lower intensity stimuli. The results suggest that reduced responsivity to pain in major depression may reflect sensory as well as affective abnormalities. Complaints of pain are very common in mood disorders, and continued examination of experimental pain in individuals with these disorders has the potential to enhance our understanding of this phenomenon.

The dimensions of pain: a multidimensional scaling comparison of cancer patients and healthy volunteers

&NA; This paper presents a new approach to the measurement and understanding of clinical pain. A multidimensional scaling (MDS) procedure was used to analyze pairwise similarity judgments made to 9 pain descriptors by 24 cancer pain patients and 24 healthy volunteers. The question was whether the dimensions of the global pain space differed between the 2 groups. The Pain Intensity dimension was found to be primary for the patients, but much less important for the volunteers. Otherwise, the group stimulus space revealed broadly similar 3‐dimensional solutions. The Pain Intensity dimension placed Mild Pain and Annoying at one pole and Intense and Unbearable Pain at the other. The Emotional Quality dimension grouped the descriptors Sickening and Miserable (and, in part, Intense Pain and Unbearable Pain) at the strong negative affect pole for both groups; they differed, however, with respect to the moderate affect pole. The Somatosensory dimension ranged from Burning to Cramping. The subject weight space revealed that the Pain Intensity dimension was the most important dimension for the patients, while Emotional Quality was more salient for the volunteers. Wide differences were found in the salience of the various dimensions to different individuals; this information may prove useful for tailoring patient treatment. The study demonstrates that MDS procedures such as INDSCAL, in which the subjects (rather than the researcher) determine the number and characteristics of the global pain dimensions, will improve our understanding and treatment of pain.

Affective deficits and pain insensitivity in schizophrenia

Affective deficits have long been considered a prominent feature of schizophrenia and play a central role in recent theory and research on the pathophysiology of this disorder. However, it has recently been argued that current approaches to the conceptualization and assessment of affective flattening in schizophrenia are confounded by the social and neuromotor deficits that are also prevalent in this disorder. Insensitivity to pain in individuals with schizophrenia — a phenomenon that has been reported frequently but never systematically investigated — provides one approach to examining affective flattening unconfounded by social and neuromotor deficits. Two studies are described in which signal detection theory measures of thermal pain sensitivity were examined in patients with schizophrenia, mood disorder, and normal controls; in addition, in the patients with schizophrenia, the relationships between these measures and measures of affective deficits were examined. Patients with schizophrenia had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but did not differ from controls with respect to their response criterion for reports of pain; patients with mood disorder had a significantly higher (i.e., more stoical) criterion for reports of pain than controls. As predicted, among the patients with schizophrenia, higher response criterion was significantly correlated with greater affective flattening and less intense affective experience (as well as with fewer positive symptoms and poorer premorbid adjustment). The results of these studies suggest that pain insensitivity in schizophrenia may reflect affective as well as sensory abnormalities, and that pain insensitivity in schizophrenia may provide a method for studying affective flattening in this disorder that is relatively independent of the social and neuromotor deficits that confound existing measures of this symptom. Continued examination of the relationship between pain insensitivity and affective deficits in schizophrenia is also important because numerous clinical reports have suggested that pain insensitivity is detrimental to health and can have life-threatening consequences in individuals with this disorder.

Altered pain and visual sensitivity in humans: the effects of acute and chronic stress.

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Analgesic Action and Pharmacokinetics of Morphine and Diazepam in Man: An Evaluation by Sensory Decision Theory

The analgesic actions of intravenously administered morphine, 0.14 mg/kg, diazepam, 0.14 mg/kg, and saline solution, 10 ml, were studied in three groups of volunteers by observing their responses to thermal stimulation for approximately four hours. Serum concentrations of morphine, determined by rad

Effects of Moderate and High Doses of Marihuana on Thermal Pain: A Sensory Decision Theory Analysis

Abstract: Sixteen habitual marihuana users, selected for their good mental and physical health, were hospitalized for three months in the New York State Psychiatric Institute. During the first month, the subjects were drug free; during the second month, they smoked marihuana cigarettes provided by NIDA (2% THC, 20 mg per cigarette) at the rate of 3 to 12 a day. A modified Hardy‐Wolff dolorimeter was used to present 20 thermal stimuli of 30‐second duration in a random manner at nine different intensities. Subjects responded from a 14‐category scale, and data were analyzed according to sensory decision theory analysis. During the third month, the subjects were again drug free. At the noxious thermal intensities, there was a decrease in the pain report criterion during the first two weeks of smoking. The pain enhancement effect was followed by return to the presmoking pain level during weeks 3 and 4 and in the postsmoking period, indicating that tolerance had developed. There was also an increase in pain discriminability during the four weeks of smoking which extended for one week after smoking. Tolerance developed to the pain report criterion but not to the thermal discriminability. This study suggests that marihuana may have hyperalgesic activity and probably enhances the perception of pain, in moderate smokers. In contrast, heavy smoking had little effect on discriminability and caused an increase in the pain report criterion.