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Biomedical subjects

Donald D Price

Publications and source records attributed to Donald D Price.

At least 73 records · Page 4Linked to original sources
PubMed1995

The development of morphine tolerance and dependence is associated with translocation of protein kinase C.

The development of tolerance to the analgesic effects of morphine as well as morphine dependence were greatly reduced by co-administration with morphine of GM1 ganglioside, a substance reported to block the translocation of protein kinase C (PKC) from cytosol to membrane of neurons. Rats made tolerant to intrathecal administration of morphine showed increased membrane-bound PKC in the superficial layers (laminae I and II) of the spinal cord dorsal horn but not in deeper layers. This increase was prevented by co-administration with morphine of GM1 ganglioside. These results indicate that the translocation and activation of PKC may be a critical step in the development of opiate tolerance and dependence. Modulation of PKC translocation and activation may prove useful for the management of pain and opiate addiction.

Animals↗
PubMed1995

Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions.

Over the last several years, compelling evidence has accumulated indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. Such neuronal plastic changes may involve activation of central nervous system excitatory amino acid (EAA) receptors, subsequent intracellular cascades including protein kinase C translocation and activation as well as nitric oxide production, leading to the functional modulation of receptor-ion channel complexes. Similar EAA receptor-mediated cellular and intracellular mechanisms have now been implicated in the development of tolerance to the analgesic effects of morphine, and a site of action involved in both hyperalgesia and morphine tolerance is likely to be in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance, two seemingly unrelated phenomena, may be interrelated by common neural substrates that interact at the level of EAA receptor activation and related intracellular events. This view is supported by recent observations showing that thermal hyperalgesia develops when animals are made tolerant to morphine antinociception and that both hyperalgesia and reduction of the antinociceptive effects of morphine occur as a consequence of peripheral nerve injury. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.

Animals↗
PubMed1994

The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man.

Oral doses of dextromethorphan (DM), a common cough suppressant and N-methyl-D-aspartate (NMDA) receptor antagonist, and their vehicle control were given on a double-blind basis to normal volunteer human subjects who rated intensities of first and second pain in response to repeated painful electric shocks and repeated 52 degrees C heat pulses. Doses of 30 and 45 mg, but not 15 mg, were effective in attenuating temporal summation of second pain, a psychophysical correlate of temporal summation of C afferent-mediated responses of dorsal horn nociceptive neurons, termed 'wind-up'. By contrast, neither first nor second pain evoked by the first stimulus in a train of stimuli were affected by any of these doses of DM. These results further confirm temporal summation of second pain as a psychophysical correlate of wind-up by providing evidence that DM selectively reduces temporal summation of second pain, as has been shown for wind-up.

Adult↗
PubMed1994

A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales.

Numerical rating scales and mechanical visual analogue scales (M-VAS) were compared for their capacity to provide ratio scale measures of experimental pain. Separate estimates of experimental pain sensation intensity and pain unpleasantness were obtained by each method, as were estimates of clinical pain. Orofacial pain patients made numerical scale and VAS ratings in response to noxious thermal stimuli (45-51 degrees C) applied for 5 sec to the forearm by a contact thermode. The derived stimulus-response function was well fit as a power function only in the case of sensory M-VAS. The power function derived from sensory M-VAS ratings predicted temperatures chosen as twice as intense as standard temperatures of 47 degrees C and 48 degrees C, thereby providing evidence for ratio scale characteristics of M-VAS. The stimulus-response function derived from sensory numerical ratings differed from that obtained with M-VAS and did not provide accurate predictions of temperatures perceived as twice intense at 47 degrees C or 48 degrees C. Both M-VAS and numerical rating scales produced reliably different stimulus response functions for pain sensation intensity as compared to pain unpleasantness and both provided consistent measures of experimental and clinical pain intensity. Finally, both mechanical and pencil-and-paper VAS produced very similar stimulus-response functions. The ratio scale properties of M-VAS combined with its ease of administration and scoring in clinical settings offer the possibility of a simple yet powerful pain measurement technology in both research and health care settings.

Adult↗
PubMed1993

Analysis of gender effects on pain perception and symptom presentation in temporomandibular pain.

Based on clinical populations, chronic orofacial pain of temporomandibular disorders (TMD) occurs more frequently (range: 2:1 to 9:1) in women than men. The reasons for this difference are not clear. The present study evaluated symptom presentation, sensitivity to pain, personality, and illness behavior in 2 samples of patients suffering with orofacial pain. Also, pain responses were studied in pain-free volunteers, controlling for experimenter-gender effects. The results showed few gender differences based on ratings of chronic or experimental pain, pain-related illness behavior, and personality. The higher ratio of women versus men seeking TMD care is consistent with greater health awareness or interest in symptoms by women than by men.

Adolescent↗
PubMed1993

The roles of spatial recruitment and discharge frequency in spinal cord coding of pain: a combined electrophysiological and imaging investigation.

An investigation was conducted to examine both temporal and spatial factors likely to be involved in spinal cord nociceptive coding by wide cord nociceptive neurons. Three separate methodologies were employed. First, the impulse frequency responses of L4 spinal cord wide-dynamic-range (WDR) neurons to gentle mechanical stimulation, vigorous but innocuous brushing, warmth (43 degrees C), and nociceptive thermal stimuli (45-49 degrees C) were electrophysiologically characterized in unanesthetized, spinal cord-transected rats. Second, the spatial distribution of evoked activity in response to the same types of mechanical and thermal stimuli was examined utilizing the 14C-2-deoxyglucose (2-DG) metabolic mapping method in the same type of animal preparation. Finally, the contributions of impulse frequency and numbers of neurons activated to encoding the distinction between painful and non-painful sensations were directly evaluated by electrically stimulating axons within the spinal cord anterolateral quadrant (ALQ) of conscious human subjects. Electrophysiological findings revealed that vigorous but innocuous brushing produced intermediate rates of impulse discharge significantly greater than those produced by 35 and 43 degrees C stimuli, yet indistinguishable from those produced by relatively low nociceptive temperatures (45-47 degrees C). Thus, the discharge frequencies of individual dorsal horn WDR neurons alone do not provide sufficient information to encode the distinction between innocuous and low intensity nociceptive stimuli. Mapping of spinal cord activity by the 2-DG method revealed that nociceptive stimuli activated extensive rostro-caudal regions extending from L1-L5. In contrast, vigorous but innocuous brushing evoked metabolic activity that was confined to a narrow zone within L3. Thus, as predicted from previous studies, the distinction between nociceptive and non-nociceptive sensory events may be encoded, in part, by differences in the spatial distribution, and hence, the relative numbers of spinal cord neurons activated by nociceptive and innocuous stimuli. The responses of conscious human subjects to varying frequencies and intensities of electrical ALQ stimulation clarify the significance of the large numbers of spinal cord neurons activated by nociceptive stimuli. With stimulus frequency held constant at 50 Hz, low stimulus currents, sufficient to activate only small numbers of ALQ axons, produced innocuous sensations. Higher stimulus currents, sufficient to activate larger numbers of neurons, consistently produced painful sensations. Increasing ALQ stimulus frequency at currents subthreshold for pain or increasing stimulus currents at frequencies subthreshold for pain resulted in painful sensations, thus indicating that both discharge frequency and numbers of neurons activated are both important factors in the encoding of pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

A canonical correlation analysis of the influence of neuroticism and extraversion on chronic pain, suffering, and pain behavior.

The relationship between neuroticism and extraversion on the 4 major stages of pain processing, that of pain sensation intensity, pain unpleasantness, suffering, and pain behavior, were studied in 205 chronic pain patients (88 male and 117 female). Patients underwent psychological evaluation which included the Pain Experience visual analogue scales (VAS) (Price et al. 1983), NEO Personality Inventory (NEO-PI) (Costa and McCrae 1985), and the Psychosocial Pain Inventory (PPI) (Getto and Heaton 1980). Canonical correlation was used to control for pain sensation intensity in evaluating affective dimensions of pain and to control for neuroticism in assessing effects of extraversion on different stages and dimensions of pain. Neither neuroticism nor extraversion were related to pain sensation intensity. Only neuroticism was associated with pain unpleasantness. Personality factors had their greatest impact on stages 3 (suffering) and 4 (illness behavior) of pain processing. The results of multiple regression analyses indicated that life-long vulnerability to anxiety and depression is paramount in understanding the relationship between personality and suffering in chronic pain. These findings provide support for the idea that personality traits influence the ways in which people cognitively process the meanings that chronic pain holds for their life, and hence the extent to which they suffer.

Adult↗
PubMed1992

Pretreatment with gangliosides reduces abnormal nociceptive responses associated with a rodent peripheral mononeuropathy.

A peripheral mononeuropathy was produced in adult male rats by placing loosely constrictive ligatures around the common sciatic nerve. As reported by others, this procedure reliably results in postoperative behavior indicative of hyperalgesia, allodynia, and potentially, spontaneous pain. In these experiments, thermal hyperalgesia was assessed by measuring foot-withdrawal latencies to radiant heat aimed at the plantar surface of rat hind paws. Behaviors potentially indicative of spontaneous pain were assessed by rating spontaneous hind paw guarding positions. Rats with sciatic nerve ligation were divided into 5 groups (n = 6/group). Three groups received injections (i.p.) of either 10, 20 or 40 mg/kg of cerebral ganglioside mixture, GA. The 4th group was injected with 10 mg/kg of the purified ganglioside GM1, and the 5th group received an equal volume of saline. All injections were given daily for 2 days before surgery, the day of surgery and 9 days after surgery. All animals were behaviorally assessed for 2 days prior to surgery, the day of surgery, as well as 1, 3, 5, 7, and 10 days afterwards. All 5 groups had significantly reduced latencies to hind paw withdrawal on the side ipsilateral to sciatic nerve ligation. However, these hyperalgesic responses were significantly attenuated in rats receiving GA or GM1 pretreatment. These data suggest that this animal model of peripheral neuropathic pain is sensitive to pharmacological manipulations useful for understanding mechanisms of neuropathic pain, including mechanisms related to excitotoxic processes. Such studies could lead to development of clinical approaches to treat this disorder.

Animals↗
PubMed1992

Spatial patterns of spinal cord [14C]-2-deoxyglucose metabolic activity in a rat model of painful peripheral mononeuropathy.

Spatial patterns of spinal cord glucose metabolic activity were examined in unanesthetized rats with painful peripheral mononeuropathy produced by sciatic nerve ligation (chronic constrictive injury, CCI). Spinal cord metabolic activity was assessed 10 days after nerve ligation by using the fully quantitative [14C]2-deoxyglucose technique. This technique allows simultaneous examination of both neural activity inferred from local glucose utilization and its spatial distribution in multiple spinal regions previously implicated in nociceptive processing. Rats used in the experiment exhibited thermal hyperalgesia to radiant heat applied to the hind paw ipsilateral to nerve ligation and behaviors indicative of spontaneous pain. Sciatic nerve ligation produced a significant increase in spinal cord metabolic activity in four sampling regions (laminae I-IV, V-VI, VII and VIII-IX) of lumbar segments compared to sham-operated rats. The pattern of altered metabolic activity in CCI rats presented 3 distinct features. (1) The spinal cord grey matter both ipsilateral and contralateral to nerve ligation exhibited substantial increases in metabolic activity compared to sham-operated rats. (2) This increase in metabolic activity was somatotopically specific, i.e., higher metabolic rates were observed on the side ipsilateral to nerve ligation than on the contralateral side, and higher metabolic rates were seen in the medial portion of the ipsilateral spinal cord dorsal horn than in the lateral portion. The peak metabolic activity occurred in laminae V-VI of CCI rats, a region involved in nociceptive processing. (3) The increase in spinal cord metabolic activity of CCI rats extended from lumbar segment L1 to L5 in all 4 sampling regions. The substantial increase in metabolic activity in both the ipsilateral and contralateral spinal cord that occurs over an extensive rostro-caudal area in CCI rats may represent a unique pattern of spinal cord metabolic activity distinct from that observed in rats exposed to acute thermal pain. This pattern of spinal cord neural activity in CCI rats may reflect possible radiation of neuropathic pain. In addition, the procedure of curare-induced paralysis in a separate group of CCI rats did not change the extent and patterns of metabolic activity seen in non-paralyzed CCI rats, reflecting a minimal influence of the afferent feedback from flexor motor reflexes on spinal cord metabolic activity following sciatic nerve ligation. This chronic increase in spinal cord neural activity in the absence of overt peripheral stimulation suggests a spinal cord hyperactive state and may account for behaviors suggestive of spontaneous pain in CCI rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Sensory testing of pathophysiological mechanisms of pain in patients with reflex sympathetic dystrophy.

The incidence of 3 sensory abnormalities was studied among 17 patients with a diagnosis of reflex sympathetic dystrophy (RSD) and 14 patients with persistent limb pain following trauma; the extent to which the 3 abnormalities were associated with each other and with the intensity of spontaneous clinical pain were also studied. These abnormalities included (1) heat-induced hyperalgesia (54.8% of 31 patients tested); (2) low-threshold A beta-mediated (45.2%) or high-threshold (54.8%) mechanical allodynia; and (3) slow temporal summation of mechanical allodynia (10 of 29 patients tested). These 3 sensory abnormalities occurred to widely varying extents and were not reliably associated with each other. As hypothesized, patients with temporal summation had significantly more intense spontaneous pain than those who did not demonstrate this sensory characteristic. In contrast, the presence or absence of thermal hyperalgesia and type of allodynia did not appear to influence the intensity of spontaneous pain. These results indicate that variable types of primary afferents (i.e., A beta versus A delta, C) and/or varying extents of abnormal spatial summation mechanisms trigger pain responses among RSD patients and that at least one of these, slow temporal summation, is likely to contribute to the intensity of a patient's ongoing pain.

Adult↗
PubMed1990

An emotional component analysis of chronic pain.

The present study sought to determine the relative contribution of frustration, fear, anger and anxiety, to the unpleasantness and depression pain patients experience. Sixty-nine women and 74 men, with an average age of 47 years, were included. Patients underwent psychological evaluation which included use of the Minnesota Multiphasic Personality Inventory (MMPI), Beck Depression Inventory (BDI), and 7 visual analog scales (VAS) measuring degree of emotional unpleasantness, pain intensity, anxiety, frustration, fear, anger and depression. Test-retest reliability coefficients were significant for the negative feeling VAS yielding an average reliability coefficient of 0.82. Analyses relating the negative feeling state VAS to pain unpleasantness and depression indices from the MMPI (scale 2) and BDI (sum score) yielded significant canonical correlations. Multiple regression was used to clarify the relationships between negative feeling VAS, pain-related unpleasantness, and indices of depression. After statistically controlling for intensity of pain, anxiety and frustration predicted unpleasantness. Regression analyses indicate that anger is an important concomitant of the depression that pain patients experience. The results suggest that anger and frustration are critical concomitants of the pain experience. Treatment techniques specifically targeting anger and frustration in these patients may prove efficacious.

Adult↗
PubMed1989

Effects of extraversion and neuroticism on experimental pain, clinical pain, and illness behavior.

The effects of 2 personality traits, extraversion and neuroticism, on experimental and clinical pain were characterized in a group of myofascial pain dysfunction (MPD) patients. Extraverts did not differ from introverts in visual analogue scale (VAS) sensory or VAS affective ratings of graded 5-sec nociceptive temperature stimuli (43-51 degrees C) nor in VAS sensory-VAS affective relationships related to their clinical pain. However, high extravert patients scored lower on affective inhibition (Pilowsky Illness Behavior Questionnaire; IBQ) compared to low extravert patients. This result is consistent with previous suggestions that extraverts inhibit overt expressions of suffering less than do introverts. High neurotic patients did not differ from low neurotic patients in their VAS sensory ratings of either experimental or clinical pain. Their VAS affective ratings of both types of pain were marginally higher as compared to low neurotic patients. As hypothesized, high neurotic score patients gave higher VAS ratings of emotions related to suffering and scored higher on items related to affective disturbance on the IBQ as compared to low neurotic score patients. Overall, the results indicate that the personality traits of neither extraversion nor neuroticism affect sensory mechanisms of nociceptive processing but appear to exert their influence by means of cognitive processes related to the ways in which people constitute the meanings and implications of pain.

Behavior↗
PubMed1989

Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block.

Patients with sympathetically maintained pain (SMP) were tested with noxious heat pulses, innocuous mechanical stimuli, and transcutaneous electrical nerve stimulation before and during local anesthetic sympathetic blocks that relieved their pain. The perceived intensity of the pain evoked by these stimuli was measured by the patients' responses on a visual analog scale and compared to the responses obtained when the same stimuli were applied to contralateral normal skin. In 5 of 7 patients tested, graded noxious heat stimuli (43-51 degrees C) applied to painful skin resulted in heat-pain intensity ratings that were essentially identical to the responses obtained when the same stimuli were applied to the normal side. Of the remaining two patients, one was clearly hypoalgesic for heat-pain and the other was probably hyperalgesic. The normal and subnormal heat-evoked responses obtained from abnormal skin were unchanged during completely successful sympathetic blocks. Trains of noxious heat pulses (52 degrees C) evoked summation of the second pain sensation in each of the 4 patients tested. This summation effect was normal and unaffected by a sympathetic block. Four of the patients had allodynia evoked by mechanical stimulation. In each of the 3 allodynia cases tested, transcutaneous nerve stimulation at an intensity that was at threshold for detection evoked burning pain and a coexistent sensation of tingle, indicating that both sensations were due to the activation of A beta axons. Patients without touch-evoked pain reported that electrical stimuli at threshold for detection produced only the sensation of tingle. The pains evoked by touch and by threshold-strength nerve stimulation were eliminated during sympathetic block. In patients with allodynia, trains of gentle mechanical stimuli and trains of threshold-strength electrical nerve stimuli produced summation of the intensity of the burning pain sensation when the stimuli were presented at 0.3 Hz. These results add to a growing body of evidence indicating that the touch-evoked pain of some patients is due to abnormal central activity evoked by input from A beta low-threshold mechanoreceptors. The coexistence of A beta-evoked pain with normal heat-evoked pain and normal heat-pain summation suggests that the central abnormality cannot be a simple hypersensitivity of wide-dynamic-range neurons. The effect of sympathetic blockade on A beta-evoked pain and its summation suggests that the crucial sympathetic interaction may take place centrally. The results show that there is considerable heterogeneity of sensory abnormalities among patients with SMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Effects of heterotopic conditioning stimuli on first and second pain: a psychophysical evaluation in humans.

Psychophysical experiments were carried out on 7 human participants to determine the extent to which experimentally produced first or second pain is reduced by concomitant nociceptive stimulation of body regions remote from those at which test stimuli are presented. This form of pain reduction has been termed diffuse noxious inhibitory controls (DNIC). Test stimuli used to evoke first and second pain consisted of intense electrical pulses delivered to the ankle area by subepithelial electrodes. Conditioning stimuli were 10 sec thermal stimuli (43, 47, 51 degrees C) applied to 1 cm2 areas of skin of either the dorsal surface of the contralateral foot or the abdominal region. The perceived magnitudes of first and second pains evoked by test stimuli were rated on visual analogue scales (VAS). Frankly noxious conditioning thermal stimuli (47 and 51 degrees C), but not innocuous thermal stimuli (43 degrees C), applied to the contralateral foot or abdomen reliably inhibited both first and second pain. However, the degree of inhibition was significantly greater for second pain that for first pain. In addition, the inhibitory effects did not outlast the duration of the conditioning stimulus. All of these results closely parallel electrophysiological observations about DNIC in primates. Since the extent of reduction of first pain is relatively weak and the durations of all inhibitory effects are very brief, it is unlikely that DNIC subserves the functions of relieving pain or providing a mechanism of coding pain. The spatial and temporal pattern of DNIC indicates that it may be a phenomenon associated more with the organization and production of withdrawal reflexes than with the relief of pain or pain coding.

Adult↗
PubMed1986

A simultaneous comparison of fentanyl's analgesic effects on experimental and clinical pain.

Intravenous administration of 0.8 microgram/kg and 1.1 micrograms/kg fentanyl in low back pain patients reduced both sensory intensity and unpleasantness visual analogue scale (VAS) responses to experimental pain evoked by graded 5-sec nociceptive temperature stimuli (45-51 degrees C) as well as VAS-sensory and VAS-affective responses to clinical pain. Fentanyl produced similar decreases in VAS-sensory responses to experimental and clinical pain. Fentanyl produced nearly equal reductions in VAS-sensory and VAS-affective responses to experimental pain but greater reductions in clinical pain VAS-affective as compared to clinical pain VAS-sensory responses. This interaction of type of pain (experimental versus clinical) and pain dimension (sensory versus affective) results from either a steeper sensory intensity-unpleasantness relationship for clinical pain as compared to experimental pain or additional selective influences of opiates on affective factors uniquely related to clinical pain. These results indicate that low to moderate doses of opiates reduce both sensory and affective dimensions of pain and strongly suggest that changes in pain affect occur mainly as a direct consequence of reductions in pain sensation intensity.

Affect↗
PubMed1983

The validation of visual analogue scales as ratio scale measures for chronic and experimental pain.

Visual analogue scales (VAS) of sensory intensity and affective magnitude were validated as ratio scale measures for both chronic and experimental pain. Chronic pain patients and healthy volunteers made VAS sensory and affective responses to 6 noxious thermal stimuli (43, 45, 47, 48, 49 and 51 degrees C) applied for 5 sec to the forearm by a contact thermode. Sensory VAS and affective VAS responses to these temperatures yielded power functions with exponents 2.1 and 3.8, respectively; these functions were similar for pain patients and for volunteers. The power functions were predictive of estimated ratios of sensation or affect produced by pairs of standard temperatures (e.g. 47 and 49 degrees C), thereby providing direct evidence for ratio scaling properties of VAS. Vas sensory intensity responses to experimental pain, VAS sensory intensity responses to different levels of chronic pain, and direct temperature (experimental pain) matches to 3 levels of chronic pain were all internally consistent, thereby demonstrating the valid use of VAS for the measurement of and comparison between chronic pain and experimental heat pain.

Acupuncture Therapy↗