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Biomedical subjects

Richard H Gracely

Publications and source records attributed to Richard H Gracely.

At least 19 recordsLinked to original sources
PubMed1998

Sensory changes in the territory of the lingual and inferior alveolar nerves following lower third molar extraction.

Post-injury inflammation activates nociceptive systems and recruits normally non-nociceptive afferents into a pain processing role. During inflammation, Abeta low threshold mechanoreceptor afferents that usually mediate tactile sensation acquire properties of nociceptors, allowing them to participate in post-injury spontaneous pain and evoked abnormalities such as tenderness and pain to light touch. This study assessed the sensory consequences of post-injury inflammation following extraction of a single, lower third molar tooth. Extensive bilateral evaluations were performed in the territory of nerves assumed to be exposed to both inflammation and mechanical trauma, inflammation alone, or only the central consequences of peripheral inflammation. Testing at the distal termination of nerves assumed to be exposed to local inflammation (mental and lingual nerve territory) revealed decreased detection thresholds (P < 0.05) to electrical stimulation and to mechanical stimulation by sensitive, disposable filaments developed and validated for this application. Testing at sites of assumed inflammation and mechanical trauma (mental nerve territory) showed reduced pain thresholds to electrical stimulation. Thermal detection and pain thresholds were not altered at any location in patients, and no effects were observed in control subjects receiving only local anesthetic injections. These results in humans are consistent with recent experimental evidence that inflammatory processes alter the central consequence of activity in large-diameter Abeta touch primary afferents evoked under natural conditions by gentle mechanical stimulation. These effects result in hyperesthesia, increased sensitivity to light touch, and mechanical allodynia, pain evoked by normally innocuous stimulation of Abeta primary afferents.

Adolescent↗
PubMed1998

The meaning of pain: cancer patients' rating and recall of pain intensity and affect.

The present study investigated the influence of an increase in present pain intensity on the rating and recall of the intensity and affective dimensions of clinical pain. Thirty-two cancer patients who reported that movement caused or exacerbated their pain rated their present pain intensity and affect before and after a session of physical therapy. Subjects also rated their usual, highest and lowest pain intensity and pain affect for the previous 3 days, and were randomly assigned to make these ratings either before or after the physical therapy session. Physical therapy increased the intensity (P < 0.01) but not the unpleasantness of the pain (P > 0.05), thus demonstrating a dissociation between pain intensity and pain affect. Beliefs about pain etiology also influenced post-therapy pain ratings. Subjects (N = 11) who believed that their pain was due to cancer, rated their post-therapy pain intensity and pain affect significantly higher than those subjects (N = 21) who did not believe their pain was due to cancer (both P < 0.05). For all subjects, recall of past pain intensity and affect was positively correlated with present levels of pain intensity and pain affect (P < 0.01). Thus, recall was assimilated to present pain levels. The results demonstrate the importance of rating both the intensity and affective dimensions of pain, and suggest that the significance of clinical pain influences pain ratings. These results also suggest that research on the rating and recall of pain, particularly the affective dimension of pain, should use actual patients who are experiencing changes in their naturally occurring pain.

Adolescent↗
PubMed1995

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain.

The oxygen-15 water bolus positron emission tomography (PET) method was used to image regional brain activity in 4 patients with chronic post-traumatic neuropathic pain confined to one lower limb and in 1 patient with post-herpetic neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a statistically significant decrease in thalamic activity contralateral to the symptomatic side. Examination of the right/left ratio for all the subjects showed that the values for the patients fell at the extremes of the normal range, according to the side of the affected body part. These initial observations suggest that functional alterations in thalamic pain processing circuits may be an important component of chronic neuropathic pain.

Adult↗
PubMed1995

Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects.

The importance of N-methyl-D-aspartate (NMDA) receptor-mediated sensitization of central nervous system (CNS) neurons is well established in animal models of acute and chronic pain. A human model of central sensitization would be useful in screening new NMDA antagonists and establishing dose regimens for clinical trials in patients with pain related to sensitization of CNS neurons. We used this model to examine the effects of intravenous infusions of two centrally acting analgesics, the NMDA receptor antagonist ketamine and the morphine-like opioid agonist alfentanil. Twelve normal subjects completed a 3-session, randomized, double-blind, crossover study. From 25 to 60 min after capsaicin injection, subjects were given intravenous infusions of ketamine (mean dose: 32 mg), alfentanil (mean dose: 3075 micrograms), or saline placebo. Both drugs significantly reduced ongoing pain and pinprick-evoked hyperalgesia during the infusion. The reduction in allodynia evoked by light stroking was statistically significant only for alfentanil. Mean reduction +/- SEM relative to placebo were for ongoing pain: ketamine, 36 +/- 9%; alfentanil, 51 +/- 5%; area of pinprick hyperalgesia: ketamine, 34 +/- 7%; alfentanil, 35 +/- 7%; and area of mechanical allodynia: ketamine, 52 +/- 20%; alfentanil, 70 +/- 12%. Because the drugs were given systemically and produced side effects in all subjects, we cannot specify the site or sites of action nor conclusively rule out a non-specific 'active placebo' response as the cause for reduction of symptoms. Arguing against an 'active placebo' response, however, was the lack of analgesic effect of intravenous midazolam (mean dose; 3.4 mg, titrated to produce side effects of similar magnitude to ketamine and alfentanil) given at 145 min after capsaicin in 9 subjects who had received saline from 25 to 60 min. The results of this study suggest that neural systems sensitive to NMDA receptor antagonists and opioids participate in capsaicin-evoked pain phenomena, and support the feasibility of pharmacological studies using the intradermal capsaicin model.

Adult↗
PubMed1994

The sensation of angina can be evoked by stimulation of the human thalamus.

We have performed single-neuron recording and microstimulation in the region of the thalamic principal sensory nucleus (ventrocaudal nucleus, Vc) prior to implantation of a deep brain-stimulating electrode in a patient with pain secondary to arachnoiditis and with a past history of unstable angina. Cells located in the 16 mm lateral plane had cutaneous receptive fields on the chest wall. At and posterior to the location of these cells stimulation coincided precisely with the sensation of angina (stimulation-associated angina). The description of stimulation-associated angina was measured using a questionnaire and was identical to the patient's usual angina except that it began and terminated suddenly. Stimulation-associated angina was coincident with a tingling sensation in the leg. Clinical, hemodynamic, electrophysiologic and biochemical measures of cardiac function showed no evidence of myocardial strain or injury related to stimulation-associated angina. Since cells in the region of the principle sensory nucleus of thalamus respond to cardiac injury in animals, the present results suggest that this region mediates the sensation of angina.

Aged↗
PubMed1992

Painful neuropathy: altered central processing maintained dynamically by peripheral input.

We performed sensory assessments before and during diagnostic tourniquet-cuff and local anesthetic blocks in 4 patients diagnosed with reflex sympathetic dystrophy (RSD). All patients complained of mechano-allodynia; lightly touching the skin evoked an intense pain sensation. At detection levels, electrical stimuli were perceived as painful, suggesting that the mechano-allodynia was mediated by A beta low-threshold mechanoreceptor afferents. A beta-mediated allodynia was further supported by reaction time latencies to painful electrical stimuli at threshold for A-fiber activation and, in 1 patient, by differential cuff blocks which abolished A beta function and allodynia while thermal sensation (warm and cold) were preserved. Local anesthetic block of painful foci associated with previous trauma abolished mechano-allodynia, cold allodynia, and spontaneous pain in all patients and relieved the motor symptoms in 1 patient with tonic contractures of the toes. Tactile and thermal perception in the previously allodynic area was preserved. When the local anesthetic block waned, spontaneous pain, allodynia, and motor symptoms returned. We propose a model of neuropathic pain in which ongoing nociceptive afferent input from a peripheral focus dynamically maintains altered central processing that accounts for allodynia, spontaneous pain, and other sensory and motor abnormalities. Blocking the peripheral input causes the central processing to revert to normal, abolishing the symptoms for the duration of the block. The model accounts for sympathetically maintained (SMP) and sympathetically independent (SIP) pain. The peripheral input can be independent of sympathetic activity or driven completely or in part by activity in sympathetic efferents or by circulating catecholamines. The shared final common pathway may explain the common features of SMP and SIP.

Adult↗
PubMed1991

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial.

Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect.

Adult↗
PubMed1988

The Descriptor Differential Scale: applying psychophysical principles to clinical pain assessment.

The Descriptor Differential Scale (DDS) applies psychophysical principles to clinical pain assessment. It contains 12 descriptor items for each pain dimension assessed. For each item, subjects indicate if their pain either is equal in magnitude to that implied by the anchoring descriptor, or how much greater or lesser on a 10-point graphic scale. The method permits collection of multiple responses, reducing scaling error, and assess both pain magnitude and scaling consistency. Ninety-one patients completed the sensory intensity and unpleasantness forms of the DDS at both 1 and 2 h after surgical extraction of a lower third molar. Results show that the DDS satisfies standard psychometric criteria for reliability, objectivity and item homogeneity. The coefficients found satisfy standard psychometric criteria and improve after elimination of inconsistent profiles.

Adolescent↗
PubMed1987

Reliability and validity of verbal descriptor scales of painfulness.

Previous studies have provided information about the reliability and validity of verbal descriptor scales of sensory intensity and unpleasantness and have shown that these two dimensions can be differentially affected by pharmacological manipulations. Since the relation between these dimensions and the general term 'pain' is not known, two experiments developed a verbal descriptor scale of painfulness and compared the sensitivity of this scale to pharmacological manipulations used previously with scales of sensory intensity and unpleasantness. In exp. I, 20 subjects used cross-modality matching to both handgrip force and tone duration to quantify the amount of pain implied by verbal descriptor phrases such as 'slightly painful,' 'somewhat painful' and 'very painful.' Ratio scales of relative magnitude for each individual were highly correlated within subjects (mean r = 0.92) and between a scale from each individual and a combined scale from others in the group (mean r = 0.93). These correlations indicate agreement between individual scales; an individual's scale values were predicted equally well by that individual or by a group of similar persons. In exp. II, 4 groups of 10 subjects rated the magnitude of painful tooth pulp sensations by choosing pain descriptors from randomized lists. Seven electrical stimuli spaced between individually determined pain threshold and tolerance values were delivered in random sequence 6 times before and after double-blind intravenous infusions of placebo, 0.11 mg/kg diazepam, 0.66 microgram/kg fentanyl or a combination of the diazepam and fentanyl doses. Mean responses were reduced significantly after all active drugs but not after placebo. These results suggest that the term pain does not represent a simple combination of sensory intensity and/or unpleasantness and shows that the sensitivity to an inert placebo, an active placebo, and an analgesic can vary with the type of pain assessment procedure.

Adolescent↗
PubMed1984

Abnormal and collateral innervations of sympathetic and peripheral sensory fields associated with a case of causalgia.

A 41-year-old female developed spontaneous burning pain (causalgia) and stimulus-induced dysesthesia (allodynia) of the dorso-lateral part of her right foot following trauma. An L3 and L4 sympathectomy eliminated the spontaneous burning pain for only 1 year, but did not affect the stimulus-induced dysesthesia. We evaluated her two years post-sympathectomy with grouped sequential anesthetic blocks and sensory testing. Sympathetic blocks at L1 and L2 eliminated the burning pain and normalized heat perception from baseline hyperalgesia, indicating that the causalgia had been reactivated via more rostral sympathetic ganglia. Anesthetic block of the sural nerve eliminated both the burning pain and the stimulus-induced dysesthesia. During the sural nerve block, perception of touch and pin, but not heat, was preserved in the sural distribution. All perception was lost following subsequent block of the peroneal branches. When the peroneals were blocked first, perception of touch, pin and heat remained in the sural distribution. With peroneal block the burning pain was eliminated, but the stimulus-induced dysesthesia remained, even in the anesthetic peroneal territory. When sural block was added to the peroneal block the stimulus-induced dysesthesia was eliminated, and sensation in the sural distribution was lost. We conclude that the sural distribution received overalapping innervation for touch and pin-prick perception, but that heat perception, burning pain and the stimulus-induced dysesthesia were sural nerve dependent. Further, we were able to dissociate causalgia pain from allodynia in this patient.

Adult↗
PubMed1983

Where is the noise in SDT pain assessment?

Many applications of sensory decision theory (SDT) to pain research have used discrimination as a measure of pain or sensory sensitivity. This belief is based on the classical SDT assumption that discrimination and criterion represent separation of sensory and decision processes. This assumed separation stems from a model where all noise or variability is part of the sensory transduction mechanism. We present an alternative formulation that allows for decision variability as well as variability in sensory transduction. This formulation documented by computer simulation shows that decision variability and sensory variability are indistinguishable and that any measure of discriminability is degraded by both. Thus discriminability is influenced by both sensory and non-sensory factors. There is no way of knowing if a drug-induced change in discriminability represents an analgesic effect or a change of the observer's ability to make consistent judgments.

Decision Theory↗
PubMed1981

Masseter inhibitory periods and sensations evoked by electrical tooth pulp stimulation.

The masseter inhibitory period and sensations evoked by electrical tooth pulp stimulation were assessed in 30 human subjects. Five intensities of electrical stimuli, producing sensations varying from below sensory detection threshold to suprathreshold pain, were applied to upper central incisors. At each stimulus intensity a train of 30, 1-msec, cathodal pulses with an interpulse interval of 2 sec was applied. The averaged masseter activity evoked by the 30 pulses at a fixed stimulus intensity was compared to the quality of the sensation elicited. The threshold for the masseter inhibitory period coincided approximately with an individual's detection threshold for the tooth pulp stimulation. Three configurations of masseter inhibitory periods (single, double and merged) were produced by different stimulus intensities. However, no particular configuration was associated unequivocally with pain sensation. Increases in stimulus intensity evoked changes both in the configuration of the masseter inhibitory period and in the quality of the sensation produced. Chi square analyses showed significant, but progressively weaker, associations between: (1) masseter inhibitory period configuration and stimulus intensity; (2) quality of sensation and stimulus intensity; and (3) quality of sensation and masseter inhibitory period configuration. The weakness of the association between the quality of sensation and masseter inhibitory period configuration also was demonstrated in a double-blind study of the effects of a narcotic analgesic, fentanyl. Although the strengths of non-pain and pain sensations were reduced significantly after fentanyl, there were no changes in the masseter inhibitory periods.

Adolescent↗
PubMed1980

A validation model for verbal description scaling of human clinical pain.

Twenty-nine subjects used quantified verbal descriptors of sensory intensity (i.e., weak, mild, intense) or unpleasantness (i.e., annoying, unpleasant, distressing) to assess the intensity or unpleasantness of sensations evoked by painful electrical stimulation of the tooth pulp over a broad stimulus range, and by a natural thermal tooth pulp stimulus, cold spray applied to exposed dentin. In addition, subjects matched the intensity or unpleasantness of the sensations evoked by the natural stimulus to that of the electrical stimuli by both the Method of Limits and the Method of Constant Stimuli. Quantified verbal descriptor values of either the sensory intensity or unpleasantness of the electrical stimuli were linearly related to stimulus intensity on a log scale, indicating that the relationships can be described by power functions. The quantified verbal description of the natural thermal stimulus and the intensity of the electrical stimulus directly matched to the thermal stimulus determined the coordinates of the clinical stimulus data point. This point was close to the experimental stimulus power function, indicating that the verbal magnitude of the clinical stimulus is predicted by the verbal magnitude of the specific electrical stimulus intensity that was matched to the clinical stimulus. This consistency supports the validity of the use of quantified verbal descriptors for the assessment of both experimentally controlled noxious stimulation and uncontrolled clinical pain sensations. It also supports the validity of direct matches between clinical and experimental pain sensations and the unpleasantness of these sensations. This procedure provides a useful independent validational paradigm for clinical pain assessment.

Adolescent↗
PubMed1980

A psychophysical analysis of experimential factors that selectively influence the affective dimension of pain.

A psychophysical analysis was made of experiential factors that influence the affective but not the sensory-discriminative dimension of pain. Seven subjects made cross-modality matching responses to several dimensions of their experience. Before each stimulus, they matched line lengths to their experienced desire to avoid pain (significance) and to their perceived likelihood of avoiding it (expectation). After each stimulus, they matched line lengths to perceived sensation intensity (in some sessions) or to felt magnitudes of positive or negative feeling (in other sessions). Non-noxious (35, 42 degrees C) and noxious (45--51 degrees C) skin temperature stimuli were randomly interspersed during each experimental session. Changes in expectation were induced by preceding one-half of the noxious stimuli with a warning signal. The average responses of these subjects indicated that 45--51 degrees C noxious temperatures were felt as less unpleasant when preceded by a warning signal. In contrast, sensation magnitudes evoked by these same skin temperatures were unaffected by the warning signal. Thus, only the magnitudes of unpleasant responses are lowered by decreasing ones' expectation of avoiding pain. Analysis of individual responses revealed two distinct patterns of response changes following presentation of the warning signal. Four subjects retained the same general goal of avoiding pain and reduced their expectation of avoiding it. Their affective responses were less unpleasant during the warning signal. The remaining three subjects primarily altered their goals and not their expectations on signaled trials. Their affective responses were not modified by the signal. Subjects were instructed to arrive at their affective responses in two ways. In one session, they compared the outcome of each stmulation with what they wanted to happen (affect-result responses). In the other session, they simply focused on the pleasantness or unpleasantness of each sensation as it was experienced (affect-process responses). All subjects' affect-result responses were more positive (or less unpleasant) than affect-process responses. All of these results underscore the critical influence of expectations and the manner in which one evaluates sensations on affective responses to noxious stimulation.

Adult↗
PubMed1978

Ratio scales of sensory and affective verbal pain descriptors.

The results of two experiments show that ratio scales of sensory and affective verbal pain descriptors are valid, reliable and objective. In the first experiment, 16 subjects rated 15 sensory and 15 affective verbal pain descriptors by numerical magnitude estimation and by cross-modality matching to handgrip force. Ratio scales of sensory and affective verbal pain descriptors computed for two separate groups were highly correlated between the groups (sensory, r = 0.97; affective, r = 0.98), as well as over session (r = 0.99, 0.98). Scales based on an individual's data correlated equally with either another set of scales from the same individual (r = 0.96, 0.98) or a mean scale from a similar group (r = 0.96, 0.89). Sensory and affective verbal descriptor scales from the first experiment correlated highly (r = 0.99, 0.99) with those from the second experiment in which 40 subjects rated verbal pain descriptors by cross-modality matching to time duration and to handgrip force. The ratio responses to the verbal descriptors in both experiments demonstrated specific functional relationships found for measurable psychophysical stimuli. This result supports the validity of cross-modality matched ratio scales of verbal stimuli. The reliability of these scales is shown by the high between-session, between-group and between-experiment correlations. The objectivity is shown by the similarity of within-subject and between-subject correlations for both group and individual descriptor scales.

Adolescent↗
PubMed1978

Validity and sensitivity of ratio scales of sensory and affective verbal pain descriptors: manipulation of affect by diazepam.

The results of two experiments suggest that sensory and affective verbal descriptors provide a valid scaling method which discriminates between the sensory intensity and the affect, or unpleasantness, of electrocutaneous stimuli. Twenty-four subjects judged the sensory intensity and affect of noxious electrocutaneous stimuli by choosing verbal descriptors from randomized lists and by cross-modality matching to time duration and to handgrip force. The psychophysical functions for sensory intensity generated by the descriptor and the cross-modality functions for sensory intensity generated by the descriptor and the cross-modality methods are the same. Psychophysical functions for affect generated by thedescriptor and the cross-modality methods are different. However, only the descriptor method produces psychophysical functions for affect that are significantly different from all the sensory functions. This result suggest that only the descriptor method distinguishes between sensory intensity and affect. The discriminative power of the descriptor method is demonstrated further in an experiment in which 32 subjects rated either the sensory intensity or the affect of the electrocutaneous stimuli immediately before and after an i.v. administration of 5 mg diazepam. This common minor tranquilizer significantly lowered affective descriptor responses (P less than 0.005) without altering sensory descriptor and sensory and affective handgrip responses. These experiments indicate that sensory and affective verbal pain descriptors may be used as a valid and sensitive tool for the evaluation of pain and pain control methods.

Adolescent↗