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Biomedical subjects

D D Price

Publications and source records attributed to D D Price.

At least 55 records · Page 3Linked to original sources

Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy.

The hyperalgesia and spontaneous pain that occur following peripheral nerve injury may be related to abnormal peripheral input or altered central activity, or both. The present experiments investigated these possibilities by examining the effects of MK-801 (a non-competitive N-methyl-D-aspartate, NMDA, receptor antagonist) and bupivacaine (a local anesthetic agent) on thermal hyperalgesia and spontaneous nociceptive behaviors in rats with painful peripheral mononeuropathy. Peripheral mononeuropathy was produced by loosely ligating the rat's common sciatic nerve, a procedure which causes chronic constrictive injury (CCI) of the ligated nerve. The resulting hyperalgesia to radiant heat and spontaneous nociceptive behaviors was assessed by using a foot-withdrawal test and a spontaneous pain behavior rating method, respectively. CCI rats receiving 4 daily intraperitoneal (i.p.) MK-801 injections (0.03, 0.1, 0.3 mg/kg) beginning 15 min prior to nerve ligation exhibited less hyperalgesia (i.e., longer foot-withdrawal latencies) on days 3, 5, 7, 10, and 15 after nerve ligation as compared to those receiving saline injections. Thermal hyperalgesia also was reduced when a single MK-801 injection was given intrathecally (i.t.) onto the spinal cord lumbar segments on Day 3 after nerve ligation. This effect of postinjury MK-801 treatment was dose-dependent (2.5-20 nmol) and lasted for at least 48 h after injection. Moreover, i.t. injection of MK-801 (10 nmol) reliably lowered spontaneous pain behavior rating scores in CCI rats compared to those in the saline group. The spinal site of MK-801 action is situated within the caudal (probably lumbar) spinal cord, since i.t. injection of MK-801 (10 nmol) onto the spinal cord thoracic segments did not affect thermal hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Local↗

Regional changes in spinal cord glucose metabolism in a rat model of painful neuropathy.

Spinal cord patterns of metabolic activity in a model of neuropathic pain were assessed in unanesthetized rats by the [14C]-2-deoxyglucose (2-DG) technique. Rats used in this procedure had demonstrable thermal hyperalgesia ipsilateral to sciatic nerve ligation and ipsilateral hindpaws that were lifted in a guarded position. The latter indicated possible spontaneous pain. Sciatic nerve ligation produced significant increases in glucose utilization in the dorsal and ventral horns of both sides, with greater activity present on the ipsilateral as compared to the contralateral side. Peak activity was in laminae V-VI, a region involved in nociceptive processing. Thus, a chronic increase in neuronal activity in these regions may reflect spontaneous neuropathic pain.

Animals↗

Cholecystokinin and its antagonist lorglumide respectively attenuate and facilitate morphine-induced inhibition of C-fiber evoked discharges of dorsal horn nociceptive neurons.

Extracellular single unit recordings were made from dorsal horn nociceptive neurons of intact, urethane-anesthetized rats during controlled electrical stimulation of the hind paw. Neither local superfusion of cholecystokinin octapeptide (CCK; 6.4 pmol to 20 nmol) nor the CCK antagonist lorglumide (LGM; 145 fmol to 145 pmol) significantly altered A- or C-fiber evoked firing or spontaneous activity. Pretreatment with CCK, however, significantly attenuated, whereas LGM enhanced, morphine-induced inhibition of C-evoked firing. These findings provide further evidence that CCK functions as a selective antagonist of opioid-induced analgesia.

Animals↗

Symptom report in orofacial pain patients: relation to chronic pain, experimental pain, illness behavior, and personality.

A study was conducted to determine symptom report patterns in a heterogenous population of orofacial pain patients and to evaluate how symptom patterns relate to various dimensions of the human pain experience. Results indicated that symptoms frequently associated with chronic orofacial pain disorders can be described by four indices related to the temporomandibular joint (TMJ) and its movement; discomfort of and parafunctional activities related to the masticatory muscles; interference of pain with activities of daily living; and presence of orofacial pain unrelated to myogeneous or arthrogenous TMJ disorders. Of these four symptom indices, only the pain interference (symptom) index was related to clinical pain and illness behavior. None was related to personality. Two of the indices were influenced by diagnosis. Biomechanical symptoms and parafunctional activities appear to be insignificantly related to perceived pain intensity, pain responsiveness, illness behavior, or personality, but are related to diagnosis. The results indicated that relatively simple symptom checklists have potential utility in screening orofacial pain patients and in evaluation of treatment outcome.

Adolescent↗

Spatial distribution of nociceptive processing in the rat spinal cord.

1. Quantitative 2-deoxyglucose (2-DG) experiments were undertaken to determine the spatial distribution of nociceptive responses in the rat spinal cord. Twenty unanesthetized, paralyzed rats with T2 transected spinal cords were divided into groups (n = 4) and stimulated with non-noxious (35 degrees C) or graded noxious temperatures (45 degrees, 47 degrees, 48 degrees, and 49 degrees C). Stimulation was delivered by cyclical immersion of one hind paw in a temperature-controlled water bath. 2. When stimulation began, 50 microCi of 2-DG was injected into the rat, and timed sequential blood samples were drawn to monitor plasma glucose and 2-DG levels. On termination of stimulation, spinal cords were removed, sectioned, and prepared for autoradiography. Local rates of spinal cord metabolism were obtained by microcomputer analysis of autoradiographs. 3. Nociceptive stimulation produced increases in glucose utilization in some of the grey matter laminae previously implicated in nociceptive processing. Within the nociceptive range, 49 degrees and 48 degrees C intensities elicited significantly greater responses than did 45 degrees C stimulation. 4. The rostrocaudal spatial distribution of nociceptive responses was most extensive within laminae V-VI with stimulus-evoked metabolic activity extending 9 mm from L2-L5. Similarly, metabolic increases occurred over 7 mm within lamina VII. In contrast, metabolic activity within the upper dorsal horn (laminae I-IV) extended only 3 mm and was limited to L4. Metabolic patterns within laminae VIII-IX sharply differed from those within other laminae in that no increases occurred within L4, although regions of L3 and L5 were responsive to stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence that substance P selectively modulates C-fiber-evoked discharges of dorsal horn nociceptive neurons.

Previous studies suggest that the undecapeptide substance P (SP) functions as a primary afferent neurotransmitter or neuromodulator of nociception which may mediate the slow temporal summation ('windup') of discharges of dorsal horn nociceptive neurons elicited by repetitive stimulation of C-afferents. The present study tested this hypothesis by investigating the effects of local spinal application of SP and an SP antagonist. [D-Pro2,D-Trp7,9]-SP (DPDT), on A- and C-fiber-evoked firing of dorsal horn neurons in an intact, urethane-anesthetized rat preparation. Extracellular single unit recordings from both wide dynamic range and nociceptive specific neurons during controlled repetitive electrical stimulation of the ipsilateral hind paw indicated that SP enhanced C-evoked firing in an apparent dose-related manner (100 greater than 20 = 4 nmol), whereas DPDT inhibited C-evoked discharges with an apparent bell-shaped dose-response (20 greater than 100 = 4 nmol). Neither agent significantly altered either A-evoked or spontaneous activity. In agreement with previous investigators, morphine sulfate also selectively inhibited C-fiber-evoked firing without altering A-fiber-mediated activity, validating the selectivity of our system. These findings provide additional evidence that SP functions as a neuromodulator of primary afferent nociception, and further suggest that the effects of SP are selective to nociceptive transmission mediated by C-fibers.

Action Potentials↗

Pain perception in a man with total corpus callosum transection.

While classical and current theories of pain emphasize the critical role of central neural pathways that represent the contralateral body surface and cross within the spinal cord, the role of neural input representing the ipsilateral body surface is uncertain. In the present experiments with a complete corpus callosum-sectioned patient, both tactile and low intensity noxious stimuli (43-47 degrees C) ipsilateral to the responding cerebral hemisphere were poorly perceived and/or rated low on verbal and visual analogue scales (VAS). Surprisingly, however, high intensity noxious thermal stimuli (49-51 degrees C) were rated on verbal or visual analogue scales as very intense and unpleasant, thereby reflecting both sensory-discriminative and motivational-affective dimensions of pain. Thus, the pathways and mechanisms subserving this ipsilateral input have high thresholds for activation, but once activated are sufficient to evoke all of the critical dimensions of the experience of pain.

Adult↗

Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness.

1. Psychophysical experiments were initiated to determine the possible influence of increasing stimulus size on perceived pain intensity. Six trained human subjects (5 male, 1 female) made visual analogue scale (VAS) ratings for pain-sensation intensity and unpleasantness in response to nociceptive thermal stimuli. Test stimuli consisted of 5-s duration heat pulses (45-50 degrees C in 1 degrees increments) delivered by one, two, or three contact thermal probes (1 cm2 each) applied to the medial aspect of the anterior forearm. 2. The area of skin receiving noxious thermal stimuli was changed by randomly varying the number of thermodes activated. The effects of varying the distance between the thermal probes also were evaluated. In the first series of experiments, thermal-probe separation was kept close to 0; in subsequent experimental series, the thermodes were separated by either 5 or 10 cm. 3. In each experimental series, considerable spatial summation occurred in both pain-sensation intensity and unpleasantness dimensions of pain. This summation occurred throughout the nociceptive thermal range of 45-50 degrees C and was larger at suprathreshold temperatures (greater than or equal to 47 degrees C) than those near threshold (less than or equal to 46 degrees C). Unlike spatial summation of perceived warmth, that of pain was not characterized by systematic changes in power-function exponents but as approximately upward parallel displacements in double-logarithmic coordinates. 4. Thermal-probe separation over a range of 0-10 cm had no effects on spatial summation of pain-sensation intensity or pain unpleasantness. In contrast, increasing thermal-probe separation increased the subjects' ability to discriminate differences in stimulus size and their ability to detect correctly the number of thermal probes activated. 5. Because affective VAS ratings of unpleasantness were linearly related to, but distinctly and systematically less than, VAS ratings of pain-sensation intensity, it was clear that subjects responded quite differently to these two pain dimensions. Affective judgements were not additionally influenced by thermal probe separation and hence by the ability to perceive stimulus size or number of thermal probes activated. 6. The results indicate that powerful spatial-summation mechanisms exist for heat-induced pain. Spatial summation of pain is likely to be subserved both by local integration mechanisms at the level of single spinothalamic-tract neurons and by recruitment of central nociceptive neurons, because spatial summation of pain occurred to approximately equal extents under conditions of thermode separations over a distance of at least 20 cm.

Adult↗

An assessment of pain responses to thermal stimuli during stages of pregnancy.

A study utilizing visual analogue scale (VAS) responses to 43-51 degrees C nociceptive thermal stimuli was carried out to determine whether women demonstrate a change in pain responsiveness across stages of pregnancy. Fifteen women tested in late pregnancy, labor, and post partum showed no significant differences in VAS responses to thermal stimuli across these stages. The results indicate that no central pain inhibitory system is active during late pregnancy or labor.

Adult↗

Idiopathic trigeminal neuralgia: sensory features and pain mechanisms.

We present a case report of a patient with the typical sensory features of idiopathic trigeminal neuralgia (ITN). The pain was elicited by innocuous stimuli, summated with repeated stimulation, radiated outside the stimulus zone, referred to a distant site, persisted beyond the period of stimulation, and exhibited a variable refractory period. Unusual sensory features included multiple trigger zones that changed over time and involved all 3 trigeminal divisions. Our sensory evaluation indicated that the pain was evoked by repetitive activation of rapidly adapting, A beta, low-threshold mechanoreceptive afferents. However, activation of such mechanoreceptive afferents alone never produces pain in normal situations and often leads to a suppression of pain responsivity. The findings support the idea that the mechanism of pain in ITN involves pathophysiological mechanisms in the central nervous system. Our hypothesis is that structural and functional changes in the trigeminal system result in an alteration in the receptive field organization of wide-dynamic-range (WDR) neurons. There appears to be an alteration in the surround inhibition mechanism of these neurons leading to an expansion of their touch receptive fields. This results in touch stimuli producing activity in WDR neurons that mimics the activity produced under normal conditions by noxious stimuli. Since WDR neurons participate in the encoding of the perceived intensity of noxious stimuli, a series of punctate tactile stimuli are now perceived as localized, pin-prick or electric shock-like sensations. Similar pathophysiological mechanisms may explain, in part, the pain of peripheral neuropathies associated with postherpetic neuralgia, diabetes and causalgia.

Electric Stimulation↗

Sensory-affective relationships among different types of clinical and experimental pain.

Different types of pain patients used visual analogue scales (VAS) to rate their level of pain sensation intensity (VAS sensory) and degree of unpleasantness (VAS affective) associated with pain experienced at its maximum, usual, and minimum intensity. Women used the same VAS to rate their labor pain during early, active, and transition phases of stage I and in pushing (stage II). Consistent with the hypothesis that the affective dimension of clinical pain can be selectively augmented by perceived degree of threat to health or life, cancer pain patients and chronic pain patients gave higher VAS affective ratings as compared to VAS sensory ratings of their clinical pain, whereas labor patients and patients exposed to experimental pain gave lower VAS affective ratings compared to their VAS sensory ratings of pain. Affective VAS but not sensory VAS ratings of pain were considerably reduced when women in labor focused on the birth of the child as compared to when they focused on their pain. The results underscore the importance of utilizing separate measures of the sensory intensity versus the affective dimension of clinical pain and provide evidence that the affective dimension of different types of clinical pain is powerfully and differentially influenced by psychological contextual factors.

Adult↗

Effects of age on pain perception: thermonociception.

The effect of age on pain sensitivity is unclear. Some studies suggest a loss of pain perception with age, whereas other studies indicate either no change or an increase in pain sensitivity with age. The present study assessed perceived intensities of six levels of painful contact thermal stimuli (43 degrees C, 45 degrees C, 47 degrees C, 48 degrees C, 49 degrees C, and 51 degrees C). Magnitude estimation procedures were used, and participants were instructed to provide separate ratings for the perceived sensory intensity and the perceived unpleasantness (affective intensity) of the thermal stimuli during separate sessions. Middle-age adults showed the lowest sensory sensitivity and greatest affective pain ratings. Although results indicate a significant but small tendency for older adults to underrate low and overrate higher intensity contact heat compared with younger adults, similarities in pain perception were stronger than differences among the age groups.

Adult↗

A psychophysical analysis of morphine analgesia.

Intravenous administration of 0.04-0.08 mg/kg morphine sulfate reduced both sensory intensity and unpleasantness visual analogue scale (VAS) responses to graded 5 sec nociceptive temperature stimuli (45-51 degrees C) in a dose-dependent manner. The lower doses of morphine (0.04 and 0.06 mg/kg) resulted in statistically reliable reductions in affective but not sensory intensity VAS responses, possibly reflecting supraspinal effects on brain regions involved in affect and motivation. However, the highest dose of morphine tested (0.08 mg/kg) reduced both sensory and affective VAS responses to graded nociceptive stimuli as well as VAS sensory responses to first and second pain evoked by brief heat pulses. Morphine also had an especially potent inhibitory effect on temporal summation of second pain that is known to occur when intense nociceptive stimuli occur at rates greater than 0.3/sec. The results support current hypotheses about neural mechanisms of narcotic analgesia and further clarify the relative effects of morphine on sensory and affective dimensions of experimental pain. The derived morphine dose-analgesic response functions also provide a reference standard for quantitatively comparing magnitudes of different CNS-mediated forms of analgesia.

Adult↗

Potentiation of systemic morphine analgesia in humans by proglumide, a cholecystokinin antagonist.

Proglumide, a cholecystokinin antagonist, potentiates analgesia produced in rats by morphine and endogenous opiates, and appears to reverse tolerance in rats to opiate analgesia. Therefore, proglumide and other cholecystokinin antagonists may be clinically valuable. We have tested proglumide's possible opiate analgesic potentiating effects by examining, in volunteers, the effects of morphine and proglumide on human pain visual analogue scale responses to 45-51 degrees C skin temperature stimuli. Proglumide (50-100 micrograms intravenously) potentiated both the magnitude and duration of analgesia produced by small doses of morphine. This study provides indirect evidence for a cholecystokinin-opiate interaction in humans. Therefore, cholecystokinin antagonists such as proglumide may serve to potentiate exogenous or endogenous opiate action.

Adult↗

A psychophysical analysis of acupuncture analgesia.

A psychophysical analysis of acupuncture analgesia was carried out in which low back pain patients made visual analogue scale (VAS) responses both to their chronic pain and to different levels of experimental heat pain (5 sec exposures to 43-51 degrees C) before and after electroacupuncture. VAS (sensory) responses to chronic pain, direct temperature matches to chronic pain, and VAS (sensory) responses to experimental pain were reduced in an internally consistent manner 1-2 h after treatment. The magnitude of this analgesic response was similar for dermatomes within the region of chronic pain and acupuncture needle placement (lower back) as well as for dermatomes remote from needle placement and chronic pain (forearm). Individual patients manifested either (1) a central-inhibitory pattern of analgesia wherein experimental and chronic pain in back regions and experimental pain in forearm regions were reduced, or (2) an origin-specific pattern wherein only the chronic low back pain was reduced. Patients tested several days after treatment all manifested the latter pattern of analgesia. VAS sensory and VAS affective analgesic responses to electroacupuncture treatment showed a delayed onset (1-24 h) to maximum effect and a duration of 10-14 days. Cumulative sensory and affective analgesic effects were observed at the end of 4 months of biweekly acupuncture treatments. The results of this analysis reveal the unique spatial and temporal properties of electroacupuncture analgesia and the extent to which it is mediated by at least two different mechanisms.

Acupuncture Therapy↗

Primary afferent and sacral dorsal horn neuron responses to vaginal probing in the cat.

An analysis was made of primary afferent and dorsal horn neuron responses to stimulation of genitalia of female cats. Three types of primary afferents responded to vaginal probing. The most common type responded maximally to the on- and off-ramps of non-noxious pressure applied directly to the clitoris. A second type responded similar but to surrounding labia mucosa. The third type showed a tonic discharge during deep vaginal-cervical probing. None of the primary afferents that responded to vaginal probing exhibited after-responses to any stimulus. However, a majority (76%) of wide dynamic range dorsal horn neurons showed increased rates of firing that outlasted the duration of vaginal probing by at least 28 sec. No other type of dorsal horn neuron responded in this manner. It appears that after-responses of wide dynamic range neurons to vaginal stimulation cannot be attributed to after-responses of primary afferents or to supraspinal mechanisms but are produced by mechanisms within the spinal cord.

Animals↗