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PubMed1978

Effects of doxepin on perception of laboratory-induced pain in man.

Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4-week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.

Adult↗

PubMed1998

Perceived need for local anesthesia in tooth drilling among Anglo-Americans, Chinese, and Scandinavians.

This study explored ethnic differences in perceptions of pain and the need for local anesthesia for tooth drilling among age- and gender-matched Anglo-American, Mandarin Chinese, and Scandinavian dentists (n = 129) and adult patients (n = 396) using a systematic qualitative research strategy. Semistructured qualitative interviews determined: (a) the relative frequency of use or nonuse of anesthetic for similarly specified tooth drilling, (b) the reasons for nonuse of anesthetic as reported by dentists about their patients, and (c) the distribution of reasons for not using anesthetic. American dentists (n = 51) reported that about 1% of their adult patients did not use anesthetic compared with 90% among Chinese (n = 31) and 37.5% among Scandinavian dentists (n = 40). Of patients, Americans (n = 112) reported 6% nonuse of anesthetic for tooth drilling compared with 90% of 159 Chinese and 54% of 125 Scandinavians. Reasons among Anglo-Americans and Scandinavians were similar (ranked): the sensation was tolerable, to avoid numb feelings afterwards, and fear of injections. Danish patients were an exception; the fact that they had paid extra and out-of-pocket for anesthetic ranked second. In contrast, Chinese dentists made their decisions not to use anesthetics because they explained drilling as only a suan or "sourish" sensation, whereas injections were described as "painful." It was concluded that ethnic pain beliefs and differences in health-care systems are powerful psychosocial variables that affect pain perception and the perceived need for anesthetic.

Adult↗

PubMed1997

Cocaine and inhibition of nitric oxide synthesis produce opioid-mediated antinociception.

Cocaine and nitric oxide are known to influence the perception of pain. The present study sought to determine if the endogenous opioid peptide system participates in cocaine-induced antinociception and antinociception produced by antagonism of nitric oxide. Pain perception was measured using the hot plate test. Administration of cocaine (25 mg/kg) to male rats resulted in a significant increase in reaction time in the hot plate test, which was reversed by treatment with 3, 10, and 30 mg/kg of the opiate antagonist, naloxone. In rats that were not treated with cocaine, doses of 30 and 60 mg/kg of naloxone significantly reduced hot plate reaction Time. Treatment of animals with the nitric oxide synthase inhibitor, N omega nitro-L-arginine, produced a significant increase in response time to the hot plate, which was reversed by administration of naloxone. These data indicate that antinociception produced in the rat by cocaine appears to have a supraspinal component and to involve activation of endogenous opioid peptide activity in the brain. The results also suggest a tonic inhibition of endogenous opioid peptide activity by nitric oxide, which when antagonized, results in diminished response to pain.

Animals↗

PubMed1991

The effects of dorsal column stimulation on measures of clinical and experimental pain in man.

Despite the extensive use of dorsal column stimulation (DCS) for the control of various chronic pain conditions, most clinicians report only modest success rates. Surprisingly, there has been little placebo-controlled investigation of its efficacy for altering either clinical or experimental pain perception. The current study compared the effects of DCS to placebo stimulation on clinical pain perception, perceived intensity of painful heat stimuli and visual stimuli, and the discrimination of small changes in noxious heat intensity and in light intensity. We found that DCS, but not placebo stimulation, significantly altered ratings of spontaneous clinical pain as well as those of painful cutaneous heat. In addition, heat discrimination thresholds were increased by DCS, but not placebo. On the other hand, DCS had no effect on ratings of visual stimulus intensity nor on visual discrimination, suggesting that the DCS modulation of pain perception was not due to a general change in attention. These data indicate that DCS significantly alters pain transmission in humans. Nevertheless, the relatively small reduction in clinical pain (less than 30%) must be weighed against the invasive nature of electrode implantation.

Adult↗

PubMed2004

Perception of pain during orthodontic treatment with fixed appliances.

The aims of this study were to investigate the initial time at which pain occurs after insertion of two initial wires of different sizes, the duration of the pain, the areas affected within the mouth, the level of self-medication, the effect of this pain on daily life, and whether gender is important in the perception of pain. The study group consisted of 109 patients (52 boys, 57 girls) with a mean chronological age of 13.6 years for boys and 14.7 years for girls. Insertion of either a 0.014 or 0.016 inch wire was by random selection. Following insertion of the archwires, a questionnaire comprising a total of 49 questions was given to the patients. They described the time of initial pain in the first question, answered the next 24 questions as 'yes' or 'no', and used a visual analogue scale for the final 24 questions. No significant differences were found in terms of gender, in the perception period of initial pain as regards the areas affected within the mouth or the effect of pain on daily living when the 0.014 and 0.016 inch wire groups were compared at 6 hours, 1, 2, 3, 4, 5, 6 and 7 days. At 24 hours, which was found to be statistically significant, more pain relief was used in the 0.014 inch archwire group. The results show that in both groups, initial pain was perceived at 2 hours, peaked at 24 hours and had decreased by day 3.

Activities of Daily Living↗

PubMed2004

Pain catastrophizing and neural responses to pain among persons with fibromyalgia.

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Adaptation, Psychological↗

PubMed2006

Neural correlates of antinociception in borderline personality disorder.

CONTEXT: A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. OBJECTIVE: To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. DESIGN: Case-control study. SETTING: A university hospital. PARTICIPANTS: Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. INTERVENTIONS: Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. RESULTS: Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. CONCLUSION: The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Adult↗

PubMed1990

Development of supersensitivity to substance P in the spinal cord of the streptozotocin-induced diabetic rats.

To investigate the possible mechanisms involved in the alterations in sensitivity to pain in diabetic rats, we examined the influence of diabetes induced by streptozotocin (STZ) on the functions of the neuronal systems that contain substance P (SP) within the spinal cord. The threshold for pain perception as determined by a tail-pinch test was significantly reduced in diabetic rats. The levels of SP in the spinal cord from diabetic rats (116.9 +/- 16.3 pmol/g tissue) were significantly lower than those from the control rats (190.2 +/- 14.1 pmol/g tissue). Diabetic rats were found to have a significant increase in the number of binding sites for SP in dorsal spinal cord. The concentrations of binding sites in diabetic rats and in control rats were 102.1 +/- 17.3 fmol/mg protein and 52.6 +/- 6.6 fmol/mg protein, respectively. These data indicate that STZ-induced diabetic rats exhibit supersensitivity to SP in the spinal cord. This may be correlated, in part, with the reduction in the threshold for perception of pain in diabetic animals.

Animals↗

PubMed1985

Hemispheric specialization and the perception of pain: a task-related EEG power spectrum analysis in chronic pain patients.

At EEG power spectrum analysis, chronic pain patients showed less alpha asymmetry than normal subjects during resting conditions, independently of the aetiology of pain. This 'quasi-symmetry' remained substantially unchanged across discrete task conditions differently from normal subjects showing left hemisphere activation during verbal-mathematic tasks and right hemisphere activation during visuo-spatial tasks. When descriptive diagnosis was considered as related to alpha asymmetry, significant differences were found between 'somatogenic' and 'psychogenic' pain patients. Specifically, somatogenic pain patients conformed to normal subjects, whereas psychogenic pain patients exhibited a trend towards a reduced left hemisphere dominance or a relative right hemisphere activation during both experimental conditions. These EEG findings seem congruent with a more frequent lateralization of psychogenic pain on the left side of the body.

Adult↗

PubMed1995

Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia.

OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/- 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation.

3-Iodobenzylguanidine↗

PubMed2006

Anticipatory electroencephalography alpha rhythm predicts subjective perception of pain intensity.

UNLABELLED: This high-resolution electroencephalography (EEG) study tested the hypothesis that the suppression of rolandic alpha power before predictable painful stimulation affects the subject's subsequent evaluation of pain intensity, as a reflection of the influence of expectancy processes on painful stimulus processing. High-resolution EEG data were recorded (126 channels) from 10 healthy adult volunteers during the expectancy of a painful CO(2)-laser stimulation at the right wrist. Surface laplacian estimation enhanced the EEG spatial information content over 6 scalp regions of interest (left frontal, right frontal, left central, right central, left parietal, and right parietal areas). Spectral power was computed for 3 alpha sub-bands with reference to the individual alpha frequency peak (about 5-7 Hz for alpha 1, 7-9 Hz for alpha 2, and 9-11 Hz for alpha 3). The suppression of the alpha power before the painful stimulation [as reflected by the event-related desynchronization (ERD)] indexed the anticipatory cortical processes. Results showed maximum (negative) correlations between the alpha 2 and alpha 3 ERD amplitude at the left central area and the subjective evaluation of pain intensity (P < .001). The stronger the anticipatory alpha 2 and alpha 3 ERD, the higher the subjective evaluation of pain intensity. For alpha 3, that correlation was confirmed even when the effect of habituation across the recording session was taken into account. These results suggest that the anticipatory suppression of the alpha rhythms over the contralateral primary sensorimotor cortex predicts subsequent subjects' evaluation of pain intensity, in line with its crucial role for the discrimination of that intensity. PERSPECTIVE: This electroencephalographic study showed that anticipatory activation/deactivation of sensorimotor cortex roughly predicts subjective evaluation of pain. This motivates further investigation on possible implications for the understanding of central chronic pain. Chronic pain patients might exaggerate the anticipatory activation of sensorimotor cortex to negligible pain stimuli.

Adult↗

PubMed2006

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice.

In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.

Analysis of Variance↗

PubMed2006

Catastrophic thinking and heightened perception of pain in others.

Past research has shown that pain catastrophizing contributes to heightened pain experience. The hypothesis advanced in this study was that individuals who score high on measures of pain catastrophizing would also perceive more intense pain in others. The study also examined the role of pain behaviour as a determinant of the relation between catastrophizing and estimates of others' pain. To test the hypothesis, 60 undergraduates were asked to view videotapes of individuals taking part in a cold pressor procedure. Each individual in the videotapes was shown three times over the course of a 1min immersion such that the same individual was observed experiencing different levels of pain. Correlational analyses revealed a significant positive correlation between levels of pain catastrophizing and inferred pain intensity, r=.31, p<.01. Follow-up analyses indicated that catastrophizing was associated with a heightened propensity to rely on pain behaviour as a basis for drawing inferences about others' pain experience. Catastrophizing was associated with more accurate pain inferences on only one of three indices of inferential accuracy. The pattern of findings suggests that increasing reliance on pain behaviour as a means of inferring others' pain will not necessarily yield more accurate estimates. Discussion addresses the processes that might underlie the propensity to attend more to others' pain behaviour, and the clinical and interpersonal consequences of perceiving more pain in others.

Adult↗

PubMed2000

The role of pain anxiety, coping, and pain self-efficacy in rheumatoid arthritis patient functioning.

Anxiety about pain is increasingly recognized as one factor contributing to increased pain perception and pain behavior [McCracken, L. M., Faber S. D., & Janeck A. S. (1998) Pain-related anxiety predicts nonspecific physical complaints in persons with chronic pain. Behavior Research and Therapy, 36, 621-630; McCracken L., & Gross R. (1995). The pain anxiety symptoms scale (PASS) and the assessment of emotional responses to pain. Innovations in clinical practice: a source book, 14, 309-321]. To assess this emotional reaction to pain in chronic pain patients, McCracken, Zayfert and Gross [McCracken, L., Zayfert, C., & Gross, R. (1992). The Pain Anxiety Symptom Scale: development and validation of a scale to measure fear of pain. Pain, 50, 67-73] developed the Pain Anxiety Symptom Scale (PASS) composed of four subscales: Cognitive Anxiety, Fearful Appraisal, Escape Avoidance and Physiological Anxiety. The present study extended previous work by examining the relationship among pain anxiety dimensions, use of active and passive coping strategies and arthritis self-efficacy as predictors of functional status in 154 rheumatoid arthritis (RA) patients. Functional status was assessed using the Five-Factor Model of the Arthritis Impact Scale, 2nd ed., (AIMS2): Physical Functioning, Affective Experience, Symptoms, Social Interaction and Role Function. Hierarchical multiple regression analysis on each of the AIMS2 criterion variables showed that pain anxiety, pain and symptom self-efficacy, health status and coping strategies were able to explain between 9 and 38% of the variance in the five AIMS2 variables. The present results support the hypothesized role of pain anxiety along with previously established contributions of self-efficacy and coping strategies, in affecting physical, social, emotional and role functioning in chronic RA patients.

Activities of Daily Living↗

PubMed2000

Modified hysterosalpingography during infertility work-up: use of contrast medium and saline to investigate mechanical factors.

OBJECTIVE: To evaluate the effectiveness of modified hysterosalpingography using <3 mL amount of contrast medium followed by injection of saline to minimize the adverse effects associated with the procedure. DESIGN: For modified hysterosalpingography, 1-2 mL of water-soluble contrast medium were injected to visualize the uterine cavity, followed by injection of 10 mL of saline to check tubal patency and spillage. A control group of patients underwent hysterosalpingography with undiluted contrast medium. SETTING: Teaching hospital. PATIENT(S): Seventy-eight infertile women [study (n = 40)/control (n = 38) groups]. INTERVENTION(S): Modified and standard hysterosalpingography. MAIN OUTCOME MEASURE(S): Assessment of uterine cavity, tubal patency, and sensation of pain during modified hysterosalpingography was compared with that during standard hysterosalpingography. RESULT(S): Uterine cavity and tubal patency were properly visualized during modified hysterosalpingography. Saline pushed the contrast medium successfully from the uterine cavity through the open fallopian tubes and into the pelvic cavity. The study group reported significantly less pain than did the control group. Between-group differences were statistically significant when pain perception (no pain vs. minimal pain vs. severe pain; no pain vs. any kind of pain) was analyzed by type of adnexal pathology (bilateral passage or unilateral passage). CONCLUSION(S): Modified hysterosalpingography was sufficient to diagnose tubal and pelvic mechanical factors. The procedure was associated with a significant reduction in self-reported pain and no medical complications.

Adult↗

PubMed2002

Comparison of local anesthesia techniques during transrectal ultrasound-guided biopsies.

OBJECTIVES: To compare the effectiveness of periprostatic nerve blockade versus intrarectal lidocaine during transrectal ultrasound-guided biopsies. METHODS: A prospective randomized study was performed on 150 men requiring biopsy of the prostate. Patients were assigned to three groups: group 1 received no anesthetic, group 2 received 10 mL of 2% lidocaine gel intrarectally, and group 3 received a periprostatic injection of 5 mL of 1% lidocaine solution before undergoing prostate biopsy. Patients were asked to respond to a preprocedural and postprocedural questionnaire that consisted of four questions designed to evaluate pain perception and pain experienced, respectively, during the entire procedure. RESULTS: The mean pain scores, comparing responses from groups 2 (topical lidocaine) and 3 (periprostatic) individually with those from group 1 (control), were not statistically different for any of the preprocedural questions. The postprocedural pain scores were significantly lower in groups 2 and 3 compared with those from group 1 (control) for overall procedure impression (3.1 +/- 1.7 and 2.6 +/- 1.8 versus 3.8 +/- 1.8, respectively; P <0.05 for both). The postprocedural scores for probe insertion were significantly lower for the topical group than for the control group (2.2 +/- 1.7 versus 3.7 +/- 2.1, P <0.05) but not for the periprostatic group compared with the control group (3.0 +/- 1.9, P = 0.14). The biopsy postprocedural scores were significantly lower for the periprostatic group than for the control group (2.8 +/- 1.9 versus 4.3 +/- 1.7, P <0.05). CONCLUSIONS: Our data confirm that both techniques of local anesthesia are effective in reducing patient discomfort; however, periprostatic nerve blockade using injectable lidocaine appears to be more specific in reducing pain during the biopsy portion of the procedure.

Adult↗

PubMed2003

Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine gluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C(max) 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C(max) 114 ng/ml; range 46-189 ng/ml; morphine-3-glucuronide mean C(max) 572 ng/ml; range 257-990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4+/-2.1 min; and meaningful pain relief, achieved in five patients, 6.8+/-7.3 min to onset, mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.

Administration, Intranasal↗

PubMed1999

Acute pain threshold in subjects with chronic pain following spinal cord injury.

Studies of pain perception in patients with chronic pain have yielded contradictory results. While several studies found that acute pain threshold is raised in chronic pain subjects, others showed that these subjects exhibit a decreased pain threshold compared to pain free subjects. The aim of this study was to further examine this topic by studying pain perception in subjects with chronic pain following partial or complete spinal cord injury (SCI). We found a significant elevation of heat-pain threshold (measured above the level of lesion) in complete SCI subjects with chronic pain (CSCIP) as opposed to complete SCI subjects without pain, incomplete SCI subjects with (ISCIP) and without chronic pain and normal controls. This elevation of pain threshold was completely reversed following a complete relief of the chronic pain by DREZ lesion. Moreover, the CSCIP exhibited significantly higher scores in the McGill pain questionnaire compared to ISCIP, indicative of a more intense chronic pain perceived by these subjects. In addition, the chronic pain below the level of spinal lesion, reported by CSCIP originated from a significantly larger body area than that of ISCIP. These results indicate that a critical level of chronic pain must be perceived in order to induce an elevation in acute pain threshold.

Acute Disease↗