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PubMed1998

[What is certain in pain therapy? The analgesic potency of neuroleptics in the treatment of chronic pain. A metaanalysis].

The wide variety of therapeutic effects make neuroleptics potent drugs in the treatment of pain. Until now there has been no proof of their analgesic potency; in spite of this fact, neuroleptics are used to treat chronic pain states on the assumption that they do have analgesic potency. A metaanalysis was performed and 48 publications reviewed. Thirty-four, the majority of the studies, are case reports, retrospective analyses or non-randomised cohort studies. Most of these reports attest to a positive effect. However, only ten out of fifteen studies with a higher statistical study power describe a possible analgesic effect. None of the studies could differentiate between the effects of analgesia and sedation of the drugs used. The metaanalysis provides no evidence of intrinsic analgesic properties of neuroleptics for their use as adjuvant analgesics.

English Abstract↗
PubMed1998

[A survey of physicians' knowledge about pain therapy with strong opioid analgesics].

INTRODUCTION: The WHO analgesic ladder, including the use of strong opioid analgesics for the treatment of cancer pain, is widely accepted. However, the use of opioids for the treatment of non-cancer pain is still controversial. This study investigates doctors' medical knowledge about basic aspects of pain management. Additionally, we determined whether the deficiencies in the treatment of patients suffering from pain are based on the rigorous national narcotic control system in Germany. METHODS: We investigated the juridical and technical knowledge of physicians specializing in pain therapy by a questionnaire. During a postgraduate course the knowledge about pain therapy according to the WHO analgesic ladder and the beliefs concerning the narcotic regulations in Germany were evaluated. The survey participants were asked to rate their attitudes on a 10-point analogue scale (1=disagreement, 10=full agreement). The participants were also asked to indicate occupational criteria such as specialty, clinical practice area, and postgraduate years of practice. Descriptive statistics for the mean values were used. RESULTS: One hundred and forty-three questionnaires were completed. The majority of participants worked at departments of anaesthesiology. Some 51.1% of the participants had no specific multiple-copy prescriptions for opioid analgesics. Only 72% of the physicians knew from which governmental institution they could order multiple-copy prescriptions. In general, more doctors would prescribe opioids by the use of normal forms. The controlled substance laws were seen as an impediment by the majority of participants, without relevant differences as to their years of practice. The regulations were regarded as ineffective protection against illegal use of opioids. Treatment of pain with strong opioid analgesics was seen as beneficial for the patients. The use of strong opioids for long-term treatment was recommended, and psychological addiction was regarded as non-existent. CONCLUSION: Therapy with strong opioids is accepted practice, but significant deficits of legal and technical knowledge uphold the undertreatment of patients suffering from cancer and non-cancer pain. Patients with a legitimate need for pain relief by strong opioids are the unintended victims of tight narcotic regulations and deficits in medical education. An ease of regulatory conditions is mandatory to reduce the reluctance for prescribing opioids. On the other hand intensified continuous medical education is mandatory to reduce the undertreatment of patients with severe pain conditions.

English Abstract↗
PubMed1984

A reinvestigation of the analgesic effects induced by stimulation of the periaqueductal gray matter in the rat. II. Differential characteristics of the analgesia induced by ventral and dorsal PAG stimulation.

This study consists of a detailed analysis of the analgesic effects induced by stimulation of the various parts of the periaqueductal gray matter (PAG) in the freely moving rat. In order to characterize the analgesia, two criteria are considered: (1) the evaluation of the degree of analgesia and behavioral side effects evoked during central stimulation; and (2) the presence of post-effects. Central stimulation (50 Hz sine waves) was delivered via bipolar concentric electrodes and analgesia was quantified by the change in the vocalization threshold induced by electrical stimulation of the tail. Within the ventral PAG, the vocalization threshold increased gradually with the intensity of the central stimulation, the degree of analgesia generally being powerful. There was no relationship between the strength of the analgesic effects and the motor disturbances also produced by stimulation of this region. Antinociceptive effects generally disappeared when the stimulation ceased. Only when the intensity of the stimulation was strong enough to induce very powerful analgesic effects were post-stimulation analgesic effects noticed. Within the dorsal and dorsolateral PAG as well as in the ventral region just surrounding the aqueduct, analgesia appeared suddenly, was generally less pronounced and was always concomitant with strong aversive reactions. In contrast with the analgesia from the ventral PAG, marked post-effects were observed. These latter characteristics were also obtained from stimulation of regions located outside the PAG (colliculi, intercollicular commissure and tectum adjacent to the dorsolateral PAG) although these zones were not extensively studied. By consideration of various data in the literature, it is concluded from this study, which clearly distinguishes stimulation-produced-analgesia (SPA) from ventral PAG versus dorsal PAG, that analgesia induced from this midbrain area involves at least two different neuronal substrates. Whilst the ventral PAG seems to be more preferentially involved in pain modulation, the authenticity of 'analgesia' triggered by stimulation of aversive regions (which are widely spread over the PAG) is questioned and proposals to explain the simultaneous appearance of analgesic effects and aversion are considered.

Animals↗
PubMed1987

Cross-tolerance between analgesic low doses of morphine and naloxone in arthritic rats.

The effects of acute injections of naloxone (3-3000 micrograms/kg i.v.) and morphine (100-1000 micrograms/kg i.v.) on the vocalization threshold induced by pressure on the paw were analyzed in adjuvant-induced arthritic rats pretreated either with naloxone or with morphine administered at low doses (9 micrograms/kg s.c. and 3000 micrograms/kg s.c., respectively) over 4 consecutive days. In naloxone-pretreated arthritic rats, the paradoxical analgesic effect of low doses of naloxone was almost abolished, and the potent analgesic effects of low doses of morphine were also strongly and dose-dependently reduced. In morphine-pretreated arthritic animals, the analgesic effect of low doses of naloxone was significantly attenuated. These results attest that a cross-tolerance with low analgesic doses of morphine and naloxone can be demonstrated in these chronic suffering animals. By contrast, in rats pretreated either with naloxone or morphine, the hyperalgesic effect of naloxone produced by higher doses persisted and even was unmasked for doses which were analgesic before the pretreatment. These data emphasize the involvement of opiate receptors different in their sensitivity and/or their functions in the two opposite effects of naloxone. They also suggest that opiate receptors and endorphinergic systems differ in normal animals and animals which experience persistent pain.

Animals↗
PubMed1993

The potentiating effects of restraint stress and continuous naloxone infusion on the analgesic potency or morphine are additive.

The analgesic potency of morphine in the rat can be increased by either continuous administration of an opiate antagonist, which also increases the number of mu-opioid receptors in the brain, or by immobilization stress. To examine further the plasticity of brain opioid mechanisms, this study assessed the combined effects of continuous naloxone treatment and physical restraint on the analgesic potency of morphine. Osmotic pumps releasing 0.3 mg/kg/h of naloxone were implanted subcutaneous (SC) in two groups of rats for 7 days and empty (SHAM) pumps were implanted in two other groups. Twenty-four hours after the pumps were removed, all animals were injected with morphine in cumulative doses and tested in the tail-flick procedure. One group of naloxone-treated rats and one group of SHAM-treated rats were tested while restrained; the other two groups were tested while unrestrained. Naloxone infusion alone and restraint alone each increased significantly the analgesic potency of morphine by 1.4-fold whereas the combination of these two treatments increased analgesic potency by almost 2-fold, significantly more than either treatment alone. All animals were retested with morphine 6 days later; the analgesic potency of morphine in the SHAM groups was still potentiated by stress but the potentiating effect of the earlier naloxone infusion was no longer evident. It appears that the opioid receptors mediating stress-induced potentiation of morphine-induced analgesia can be upregulated transiently by 7-day infusion of naloxone.

Animals↗
PubMed1983

Copper salicylate as an anti-inflammatory and analgesic agent in arthritic rats.

Recent research indicates that endogenous copper is involved in anti-inflammatory and tissue repair processes. Of interest also is the analgesic efficacy of Cu complexes, since rheumatoid arthritis and similar inflammatory conditions are extremely painful. In pilot experiments, arthritic rats failed to increase voluntarily their rate of drinking a 5 mg/ml solution of copper salicylate (Cu Sal). The data from the experiment reported here showed that a forced oral dose of Cu Sal calculated at 200 mg/kg body weight significantly reduced sensitivity to mechanical pressure in less than 30 minutes but more than 15 minutes. The analgesic effect of the Cu Sal was greater for arthritic than for non-arthritic rats, suggesting that two types of analgesia are involved. First, it produces a direct analgesic effect which works irrespective of the presence of inflammation. Second, it appears to have an indirect analgesic effect due to reduction of inflammatory hyperalgesia. It was also found that Cu Sal administered orally reduces inflammation in rats with adjuvant arthritis. In summary, the results from this experiment demonstrate that Cu Sal has specific and general analgesic properties and anti-inflammatory potential.

Administration, Oral↗
PubMed1995

Unmet analgesic needs in cancer patients.

This study was designed to characterize unmet analgesic needs in a group of cancer patients. One hundred one inpatients were surveyed to document pain prevalence and intensity, satisfaction with pain control and factors associated with unmet analgesic needs during the week prior to admission. Forty-four percent had unmet analgesic needs, defined as pain of moderate or greater than moderate intensity. These patients had a significantly greater prevalence of bone and axillary node involvement, higher than pain intensity, and less satisfaction with pain control. Fifty-nine percent were satisfied with pain control. Dissatisfaction was associated with higher usual pain intensity, less satisfaction with physician information about pain etiology, less frequent attribution of pain to disease, sharp pain, constant and intermittent pain, patient perceptions of less physician concern about pain, patient and physician belief that the patient is receiving insufficient analgesic, and patient wanting more control over analgesic regimen. Patients may benefit from improved treatment of specific syndromes and by attention to communication.

Aged↗
PubMed2004

The analgesic effect induced by capsaicin is enhanced in inflammatory states.

Agonists of the vanilloid receptor type 1 (VR1), such as capsaicin, induce an analgesic effect following an initial excitatory response. It has been demonstrated that the vanilloid system plays an important role in inflammatory hyperalgesia. In accordance, we show that the VR1 antagonist capsazepine (30 microg; i.pl.) prevented the thermal hyperalgesia induced by carrageenan or complete Freund's adjuvant (CFA) in mice. Furthermore, we studied whether this inflammation-induced activation of the vanilloid system could enhance the analgesic properties of capsaicin. A single administration of capsaicin (10 microg; i.pl.) induced in control mice an analgesic effect that lasted for 2 days. In contrast, in carrageenan-treated animals, the analgesic effect of this dose of capsaicin lasted for 6 days and in CFA-treated mice for 30 days. This prolongation of capsaicin-induced analgesia during inflammation was mediated through VR1 since it was completely blocked by coadministration of capsazepine (10 microg). Licking behavior induced by capsaicin in carrageenan- and CFA-treated mice was greater than in control animals. However, although capsaicin induced a more prolonged analgesia in CFA-treated mice, the licking behavior was greater in the carrageenan-treated group, suggesting that the prolongation of analgesia is independent of the initial nociceptive input. Overall, these results show that the analgesic effects of capsaicin are importantly enhanced during inflammation, supporting the fact that the stimulation of VR1 could perhaps constitute a suitable strategy to avoid inflammatory hyperalgesia.

Animals↗
PubMed2006

Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice.

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-D-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D(1) and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.

Animals↗
PubMed2006

Parental history of chronic pain may be associated with impairments in endogenous opioid analgesic systems.

A family history of chronic pain has previously been linked to increased incidence of spontaneous acute pain and risk for chronic pain. Mechanisms underlying these associations are unknown, although similar effects on both acute and chronic pain suggest that central endogenous analgesic system differences may be relevant. This study tested whether a positive parental chronic pain history (PH+) was associated with impaired endogenous opioid analgesic responses to acute pain. Seventy-three chronic low back pain patients (LBP) and 46 pain-free controls received opioid blockade (8mg naloxone i.v.) and placebo blockade (saline) in randomized, counterbalanced order in separate sessions. During each, subjects participated in a 1-min finger pressure pain task followed by an ischemic forearm pain task, providing pain intensity ratings during and immediately following each task. To assess opioid analgesic function, blockade effects were derived by subtracting placebo from blockade condition pain responses. Placebo condition analyses indicated that both PH+ subjects and LBP subjects reported greater acute pain sensitivity than respective comparison groups (p's<.05). Multivariate analyses indicated that, beyond any influence of current chronic pain status, PH+ subjects failed to exhibit any endogenous opioid analgesia to acute ischemic pain, whereas PH- subjects elicited effective opioid analgesia (p<.05). A significant multivariate PHxSubject Type interaction (p<.05) indicated that opioid analgesic impairments were most prominent in PH+ LBP subjects. Similar analyses for finger pressure pain blockade effects were nonsignificant (p>.10). The possible heritability of endogenous opioid analgesic dysfunction observed in individuals with a positive parental chronic pain history remains to be investigated.

Adult↗
PubMed1982

An analgesic study with repeated doses of phenazone, phenazone plus dextropropoxyphene, and paracetamol, using a visual analogue scale.

A double blind randomized analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth. In a repeated dose regimen, 120 patients received one of three different analgesics: phenazone, phenazone plus dextropropoxyphene, or paracetamol. The assessments of pain were made hourly on a visual analogue scale and the evaluation was carried out according to a method which considers repeated dose intake. The analgesic efficacy of 500 mg phenazone was similar to 500 mg of paracetamol. The pain reduction seemed adequate in most patients and no statistical differences were obtained between the treatment drugs. All analgesics were taken when needed, and the time interval from end of operation to first tablet intake, as well as the pain score at first tablet intake, were factors which significantly influenced the efficacy of the drugs. Therefore, these factors may be of significant importance in the evaluation of analgesics in small sample studies.

Acetaminophen↗
PubMed2000

Numerous adrenal chromaffin cell preparations fail to produce analgesic effects in the formalin test or in tests of acute pain even with nicotine stimulation.

Previous studies have reported that intrathecal implants of a variety of adrenal chromaffin cell preparations all produce analgesic effects in rodents. The major objective of the present study was to determine if any adrenal chromaffin cell preparations produce more robust analgesic effects than other cell preparations. The present study included adult rat adrenal chromaffin tissue allografts, purified adult bovine chromaffin cells, and polymer-encapsulated calf adrenal chromaffin cells, all prepared according to previously published procedures, as well as purified calf adrenal chromaffin cells. Previous studies have also suggested that immunosuppression may play a role in graft survival, and potentially increase the magnitude of analgesic effects, so the present study included both immunosuppressed and non-immunosuppressed groups (cyclosporin A, 10 mg/kg per day). Behavioral tests included the formalin test; and a dorsal tail-flick, hot-plate, and paw-pinch test, conducted sequentially 2 min after systemic nicotine (0.1 mg/kg) to evoke release from the chromaffin cells, as previously reported. Analgesic effects related to morphine and nicotine were detected, and consistent differences in performance could be detected between individual animals. Surprisingly, no analgesic effects were detectable with any of the four chromaffin cell preparations, with or without immunosuppression, in the formalin test or with nicotine stimulation in tests of acute pain.

Acute Disease↗
PubMed1993

Postoperative narcotic analgesic administration.

The administration of narcotic analgesics to postoperative patients was examined with 180 uncomplicated adult appendectomy patients. Narcotic analgesic doses were transcribed from the hospital records of these patients for the entire postoperative period. Equianalgesic doses were calculated so that all medications were comparable with meperidine. Eighty-three percent (n = 150) of the patients received meperidine. Patients who received meperidine were given significantly more narcotic analgesics than those who received morphine sulfate. The amount of narcotic analgesics received by patients was significantly related to their length of hospital stay. Meperidine and Tylenol #3 (acetaminophen with codeine phosphate; McNeil Pharmaceutical, Spring House, PA) comprised the significantly associated analgesics. These findings suggest a need to reexamine the current use of meperidine in postoperative analgesia.

Adolescent↗
PubMed1995

Surgical cardiac patient characteristics and the amount of analgesics administered in the intensive care unit after extubation.

The study investigated relationships between patient characteristics (desire for control, perceived control, perceived social support, state anxiety, gender, weight and age) and the amount of analgesics administered in the intensive care unit after extubation. Subjects included surgical cardiac patients (n = 56) who were predominantly male (75%), Caucasian (89%) and had a mean age of 59 years. The findings showed significant positive relationships between the amount of analgesics administered and state anxiety and weight. Significant negative relationships were found between the amount of analgesics administered and desire for control, perceived control and age. Desire for control, age and state anxiety predicted the amount of analgesics administered. The findings provided insight into analgesic requirement and nursing actions.

Cardiac Surgical Procedures↗
PubMed1993

A placebo-controlled model for assaying systemic analgesics in children.

To assess the sore throat pain model in children as an assay for systemic analgesic agents in children under double-blind, placebo-controlled conditions, we conducted a single-dose parallel study that compared 10 mg/kg ibuprofen (n = 39), a new analgesic agent for children, and 15 mg/kg acetaminophen (n = 38), an approved analgesic for children, to placebo (n = 39) in children from 2 to 12 years of age with acute sore throat. At 1/2, 1, 2, 3, 4, 5, and 6 hours (2 hours in the pediatrician's office followed by 4 hours at home), children assessed pain intensity with a pain thermometer and pain relief with a smiley-face scale. The parent and pediatrician assessed pain intensity and change in pain; the parent also provided an overall evaluation at 6 hours. The children rated ibuprofen and acetaminophen as significantly effective compared with placebo (p < 0.05) on both scales at most posttreatment time points and overall. The parent and pediatrician also rated both active medications as significantly different from placebo on both of their scales (p < 0.05) at several time points and overall. On the parent's overall evaluation, ibuprofen was rated as effective compared with placebo (p < 0.05). Both active agents significantly (p < 0.05) reduced oral temperature in children with baseline temperatures > 99 degrees F. No treatment-related adverse effects were observed. We conclude that the sore throat pain model is a sensitive assay for identification of the activity of oral analgesic drugs in children and that ibuprofen is an effective analgesic in children.

Acetaminophen↗
PubMed2002

Evidence for and against the use of opioid analgesics for chronic nonmalignant low back pain: a review.

INTRODUCTION: Opioid analgesics are very effective for treating pain, but their chronic use in nonmalignant conditions is controversial. Low back pain is a common condition, and chronic low back pain (CLBP) is the most frequent regional pain syndrome in the United States. This article reviews the evidence for and against the use of chronic opioid analgesic therapy (COAT) for patients with CLBP unrelated to cancer. METHODS: A literature review was conducted looking for reports of oral or transdermal opioid analgesic therapy for CLBP. RESULTS: There are very few randomized controlled trials of COAT for CLBP. The scant evidence that is available suggests that over the short-term, COAT is helpful with patients with CLBP. In the published reports, most of which are brief in duration, COAT is associated with moderate side effects but a low risk of abuse or drug addiction. COAT was not associated with adverse long-term sequelae. Longer-acting opioid analgesics may be preferable to shorter-acting agents. Patient selection and close follow-up are critical to good outcomes. CONCLUSIONS: There is a place for the use of chronic oral or transdermal opioid analgesics in the treatment of some patients with CLBP.

Journal Article↗
PubMed2000

The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study.

The aim of this study was to assess if the pain of osteoarthritis is reduced by topical capsaicin and to determine whether addition of glyceryl trinitrate has an effect on analgesic efficacy and tolerability of capsaicin. A randomized, double blind, placebo controlled study was carried out on 200 adult patients attending a Pain Clinic with osteoarthritis pain. Patients applied one of four creams topically over the affected joint over a 6 week period. Creams contained either placebo (vehicle), 0.025% capsaicin, 1.33% glyceryl trinitrate or 0.025% capsaicin + 1.33% glyceryl trinitrate. Analgesic efficacy, tolerability of cream and analgesic consumption were assessed. One hundred and sixty-seven of 200 patients completed the study. Baseline visual analogue scores (0-10 scale) for pain were 6.40. There was a significant reduction in pain scores in the glyceryl trinitrate group (mean decrease 0.59, p< 0.05, 95% confidence limits 0.04-1.14), 0.025% capsaicin group (mean decrease 0.5, p< 0.05, 95% confidence limits 0.05-1.05) and the glyceryl trinitrate capsaicin group (mean decrease 1.1, p<0.05, 95% confidence limits 0.22-1.98). Baseline discomfort of application scores were similar for all but the capsaicin groups (they were significantly higher (by 2.1 units, p< 0.001)). The odds ratio in favour of continuing treatment was 2.1 (95% confidence limits 1.0-4.4) for glyceryl trinitrate and 2.4 (95% confidence limits 1.2-5.1) for capsaicin and 5.0 (95% confidence limits 3.8-6.4) for capsaicin GTN combination. The study showed that topical capsaicin and glyceryl trinitrate have an analgesic effect in painful osteoarthritis. When used together this effect is increased with the combination being more tolerable than capsaicin alone. Analgesic consumption is decreased by capsaicin, glyceryl trinitrate and to a greater extent by both combined.

Administration, Topical↗
PubMedDate not supplied

Analgesic effects of low-dose ropivacaine for interscalene brachial plexus block for outpatient shoulder surgery-a dose-finding study.

BACKGROUND AND OBJECTIVES: Interscalene brachial plexus block (ISB) with low-dose bupivacaine provides effective postoperative shoulder analgesia in outpatients. The analgesic effect of low-dose ropivacaine for ISB is unknown. METHODS: In this double-blind study, 66 outpatients scheduled to undergo arthroscopic shoulder surgery were randomly assigned to receive an ISB with 10 mL of 0.125%, 0.25%, or 0.5% ropivacaine before surgery. Postoperative verbal pain rating score, analgesic consumption, and the extent of motor and sensory block was assessed for 120 minutes after surgery. RESULTS: The degree of shoulder analgesia was dose dependent. Postoperative pain scores were lowest with 0.5% ropivacaine, and analgesic was not required in the hospital in 70% of the patients who received 0.25% and 0.5% ropivacaine, compared to 30% with 0.125% ropivacaine (P < .03). In the patients who required no analgesic in the hospital, the time to first oral analgesic at home was approximately 10 hours irrespective of ropivacaine concentration. Motor and sensory block distal to the elbow was detected in 25% of the patients in the 0.5% group but none in the 0.125% group. CONCLUSIONS: Interscalene brachial plexus block with low-dose ropivacaine, 10 mL of 0.25% and 0.5%, provides effective long-lasting shoulder analgesia in a majority of patients after arthroscopic surgery.

Adult↗