Intrathecal baclofen is analgesic in patients with chronic pain.
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Aged↗
Biomedical subjects
S E Abram
Publications and source records attributed to S E Abram.
Neural blockade for neuropathic pain.
OBJECTIVE: This study reviews the available literature regarding the use of nerve blocks for the management of peripheral neuropathy. DESIGN: A MEDLINE literature review was carried out, examining the existing literature about the use of nerve blocks for the treatment of mononeuropathies and radiculopathy. INTERVENTIONS: The study encompassed the use of local anesthetic peripheral and sympathetic nerve blocks, perineural steroid injections, and neurolytic blocks. RESULTS: Local anesthetic peripheral and sympathetic blocks provide useful diagnostic information but tend to afford only temporary therapeutic benefits in patients with peripheral neuropathy. Perineural steroids provide lasting relief for some patients with radiculopathy and peripheral neuropathy, but in most studies, it is a minority of patients who experience long-term relief. Peripheral neurolytic blocks are helpful for some patients with peripheral mononeuropathy, particularly in the setting of cancer pain. Although there are the risks of exacerbating pain and serious complications, certain patients experience long-term relief. CONCLUSIONS: Most discussions on the management of peripheral neuropathy do not include the use of nerve blocks. Nevertheless, the nerve block procedures discussed here can play an important role in the management of these conditions.
Autonomic Nerve Block↗
Treatment of lumbosacral radiculopathy with epidural steroids.
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Animals↗
Neural blockade for diagnosis and prognosis. A review.
On the basis of the published material reviewed above, we conclude that there are many limitations that weaken the theoretic basis for neural blockade as a diagnostic or prognostic tool. In addition, these procedures in general lack thorough documentation of clinical usefulness. Reasonable employment of diagnostic neural blockade, therefore, requires not only care in technique and confirmation of effects, but also caution in interpretation and application of the results. This critical evaluation needs to be tempered, however, by two further observations. Experienced and observant clinicians have found these procedures may, on certain occasions, provide information that is helpful in guiding subsequent therapy, so we should not be in haste to dismiss the accumulated judgment of practitioners. Finally, the confusion and complexity that typifies diagnosis in chronic pain may justify the selective use of diagnostic blocks that make anatomic and physiologic sense, even if their validity is incompletely proved.
Anesthetics, Local↗
Necessity for an animal model of postoperative pain.
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Animals↗
Assessment of the potency and intrinsic activity of systemic versus intrathecal opioids in rats.
BACKGROUND: One measure of an opioid's efficacy is its ability to retain its analgesic effect as the intensity of a noxious stimulus is increased. A few studies have assessed the ability of either spinal or systemic opioids to produce analgesia using low- and high-intensity stimulation. There are little data available to show whether there are differences in efficacy between systemic and intrathecal opioid administration. The purpose of this study was to assess the relative efficacy of several clinically useful opioids systemically and spinally and to determine whether intrathecal administration resulted in greater efficacy than systemic administration. METHODS: Groups of rats were administered multiple doses of meperidine, morphine, hydromorphone, fentanyl, sufentanil, or buprenorphine either subcutaneously or intrathecally via implanted catheters. Noxious radiant heat was applied sequentially to each hindpaw, one at low intensity (adjusted to a mean withdrawal latency of 10 s) and one at high intensity (adjusted to a mean withdrawal latency of 5 s). Paw withdrawal latencies were recorded; dose-response curves for each intensity and each route of administration were graphically recorded, and ED50s were calculated. Ratios of high-to low-stimulus intensity ED50s were calculated for both routes of administration for each drug, and the ratios of subcutaneous-to-intrathecal ED50s for low-intensity stimulation were calculated to assess the relative systemic versus spinal potencies for each drug. RESULTS: The ratios of the high-to-low intensity ED50s were meperidine, 11.8, morphine, 6.1, hydromorphone, 2.6, fentanyl, 2.3, sufentanil, 1.8, and buprenorphine, 24.0. For intrathecal administration, there was uniformity of the high- to low-intensity ED50 ratios for the agonist drugs (meperidine, 2.1; morphine, 2.1; hydromorphone, 1.9; fentanyl, 1.8; sufentanil, 1.6). For morphine and hydromorphone, the systemic ED50 doses were several hundred times the intrathecal ED50s whereas the systemic-to-spinal ED50 ratios for the other drugs were 20 or less. CONCLUSIONS: As intensity of noxious stimulation is increased, the more potent opioid agonists, administered systemically, produce antinociception with lesser increases in dose compared with lower potency drugs such as meperidine or morphine. When given spinally all opioid agonists tested, including morphine and meperidine, demonstrated good efficacy, as measured by their ability to provide antinociception for high versus low intensity stimulation.
Administration, Cutaneous↗
Adequate general anaesthesia--what are we trying to achieve?
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Anesthetics, Inhalation↗
Neural blockade for upper-extremity pain.
Carefully performed and interpreted neural blockade can be a useful adjunct in both the diagnosis and treatment of painful syndromes of the upper extremity. Pain is a very difficult entity to quantify and diagnose specifically because of its subjective nature, vast differences between patients and their response to pain, and largely because of our inexact understanding of its physiology. Best results of block therapy require thorough understanding of these complexities and limitations, and a rational, careful examination of the data it provides.
Arm↗
Intrathecal acetyl cholinesterase inhibitors produce analgesia that is synergistic with morphine and clonidine in rats.
Intrathecal (IT) administration of acetyl cholinesterase inhibitors produces analgesia through a muscarinic action. The addition of IT cholinergic agonists to IT opioids or alpha 2-adrenergic agonists results in enhanced analgesic effects, but it is not clear whether these interactions are synergistic, additive, or less than additive. Dose-response curves for hot plate and tail immersion tests were established for IT neostigmine, physostigmine, and echothiophate in rats. Dose-response curves for hot plate testing were established for IT morphine and clonidine. The effect of maximally effective doses of each of the three cholinergic drugs on hot plate testing was plotted over time. Isobolographic analysis was performed for hot plate testing using neostigmine-morphine and neostigmine-clonidine combinations. The three cholinesterase inhibitors produced profound analgesia on hot plate testing but incomplete analgesia using the tail immersion test. Duration of analgesia on hot plate testing ranged from 45 min for physostigmine to more than 24 h for echothiophate. IT administration of combinations of neostigmine plus morphine and neostigmine plus clonidine both produced significantly more profound analgesia than the calculated additive effects and are, therefore, synergistic in their actions.
Analgesia↗
Inhibition of nociception-induced spinal sensitization by anesthetic agents.
BACKGROUND: Subcutaneous injection of dilute formalin in the hind paw of the rat produces a biphasic nociceptive response. Initial C-fiber activity is accompanied by flinching of the paw for about 5 min (phase 1), followed by cessation of activity and resumption of flinching beginning 15 min after injection and lasting about 40 min or more (phase 2). The second phase depends on changes in dorsal horn cell function that occur shortly after the initial C-fiber discharge. It was previously shown that isoflurane, administered during phase 1, reduced phase 2 activity, but a combination of isoflurane and nitrous oxide given throughout phase 1 did not suppress spinal sensitization. The same model was used to determine the effects of several inhalation and intravenous anesthetic agents on phase 2 of the formalin test. METHODS: The formalin test was carried out on male Sprague-Dawley rats. Animals anesthetized briefly with halothane to facilitate formalin injection, were compared to animals that received 1 MAC anesthesia from 5 min before to 6 min after formalin injection using halothane, enflurane, isoflurane, desflurane, or 70% N2O, or a combination of nitrous oxide plus 1 MAC halothane. Animals that were given intravenous saline immediately before injection of formalin were compared to animals given either 20 mg/kg intravenous thiopental just before formalin injection or 10 mg/kg intravenous propofol just before and 3 mg/kg immediately after formalin injection. Flinches/minute were counted at 1 and 5 min after formalin injection and thereafter at 5-min intervals for 1 h. The total of 1- and 5-min flinches were considered phase 1 activity and the total of 10-60-min flinches were considered phase 2. Total phase 2 activity was compared between groups using one-way analysis of variance. RESULTS: Animals that received halothane, enflurane, isoflurane, desflurane, or nitrous oxide during phase 1 demonstrated a significant decrease in phase 2 activity when compared to controls, while those that received a combination of nitrous oxide and halothane exhibited no difference. Animals that received intravenous thiopental anesthesia during phase 1 demonstrated no difference in phase 2 activity when compared to controls, whereas those that received propofol during phase 1 demonstrated a significant decrease of phase 2 activity. CONCLUSIONS: Volatile anesthetics or nitrous oxide significantly suppress spinal sensitization, whereas the combination of nitrous oxide plus halothane causes no suppression. Thiopental does not affect spinal sensitization, whereas propofol causes significant suppression. These results may have important implications regarding the development of postoperative pain.
Analgesia↗
Characteristics of the analgesic effects and drug interactions of intrathecal carbachol in rats.
BACKGROUND: Intrathecal carbachol produces consistent analgesia in animals without appreciable adverse effects. Little is known about the ability of this drug to provide analgesia as stimulus intensity is increased. Likewise, there are few data regarding interactions between carbachol and other intrathecal analgesics. METHODS: Using two different noxious radiant heat intensities, one applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms intrathecal carbachol on paw withdrawal latencies were measured. Similar testing was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8, 1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were administered, responses to the low intensity stimulus were recorded, and the ED50 of each combination was established and isobolographic analysis of the drug interactions was carried out. RESULTS: The 30-micrograms dose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED50 (95% confidence interval) of intrathecal carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64 micrograms (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED50 values for intrathecal morphine and clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive effects. The ED50 for the carbachol-morphine combination was 12% of the expected additive value and the ED50 for the carbachol-clonidine combination was 30% of the expected additive value. CONCLUSIONS: Intrathecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing analgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine.
Analgesics, Non-Narcotic↗
Use of psychoactive substances in three medical specialties: anaesthesia, medicine and surgery.
In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.
Adult↗
Systemic opioids do not suppress spinal sensitization after subcutaneous formalin in rats.
BACKGROUND: Preemptive treatment with a combination of inhalation anesthesia plus intrathecal morphine has been shown to inhibit development of hyperalgesia that follows subcutaneous (SC) formalin injection in rats. Using a similar paradigm, this study sought to determine whether moderate doses of opioids, administered systemically, could inhibit development of a hyperalgesic state. METHODS: Flinches per minute were observed 1 and 5 min after formalin injection (phase 1) and at 5-min intervals for the remainder of 1 h (phase 2) for five groups of rats. All animals received isoflurane 1% during and for 6 min after formalin injection. Groups 1 and 2 received SC alfentanil 200 micrograms/kg or normal saline, respectively, before formalin and 0.5 mg/kg naloxone SC 6 min after formalin. Groups 3 and 4 received SC morphine 20 mg/kg or SC normal saline, respectively, before formalin and SC naloxone 0.5 mg/kg plus naltrexone 0.5 mg/kg after formalin. Group 5 received normal saline at both injection times. RESULTS: Phase 2 activity was nearly identical for the three control groups. Total phase 2 activity for group 1 (alfentanil) was 16% less than control (not significant, P > 0.05). Total phase 2 activity for group 3 (morphine) was almost identical to control. CONCLUSIONS: Administration of 1% isoflurane plus systemic opioids, administered in doses that produce profound analgesia in standard analgesic testing paradigms, do not produce the significant suppression of subsequent hyperalgesia that has been reported with inhalation anesthesia plus intrathecal opioids.
Alfentanil↗
Analgesic and neurotoxic effects of intrathecal corticosteroids in rats.
BACKGROUND: Despite the widespread use of epidurally administered corticosteroids in the treatment of sciatica and the failure of animal studies to demonstrate neurotoxicity from epidermally administered corticosteroids, controversy remains regarding the mechanism of action as well as the safety of this treatment. The goal of this study was to determine whether spinally administered corticosteroids have any analgesic effects, and whether repeated intrathecal administration causes any neuronal damage to the spinal cord. METHODS: Chronic lumbar intrathecal catheters were implanted in rats. Formalin testing was carried out 1 h after the intrathecal administration of 400 micrograms methylprednisolone sodium succinate, 48 h after intrathecal administration of triamcinolone diacetate 250 micrograms, or 24 h after the last of a series of four injections of triamcinolone diacetate 250 micrograms given at 5-day intervals. Histologic sections of multiple levels of spinal cord from the animals receiving repeat intrathecal steroid injections were compared to those from animals that received intrathecal saline at the same intervals. RESULTS: The animals receiving repeated intrathecal triamcinolone diacetate demonstrated mild, statistically significant reduction of pain behavior (hindlimb flinching) during the second but not the first phase of the formalin test when compared to controls. No analgesic effects were demonstrated after methylprednisolone sodium succinate or a single injection of triamicinolone diacetate. Animals that received methylprednisolone sodium succinate demonstrated transient segmental allodynia. No behavioral or neurologic abnormalities were seen in any other group. Some histologic evidence neuronal damage (the presence of argyrophilic neurons was seen in the chronically implanted animals in areas of the cord adjacent to the spinal catheters, but there was no difference in incidence of these changes between the steroid and control groups. CONCLUSIONS: Intrathecal steroid injections have no analgesic effect and do not suppress spinal sensitization when administered acutely. After chronic administration, there is a mild effect on nociceptor-driven spinal sensitization (phase 2 of the formalin test), but no analgesic effect on an acute noxious stimulus (phase 1 of the formalin test). Repeated intrathecal administration of triamcinolone diacetate (0.8 mg/kg) is not associated with spinal neurotoxic effects during the time period studied.
Adrenal Cortex Hormones↗
Halothane enhances suppression of spinal sensitization by intrathecal morphine in the rat formalin test.
BACKGROUND: Injection of formalin in the hindpaw of the rat induces intense C-fiber activity accompanied by brief flinching of the injected paw (phase 1) and gives rise to facilitated spinal processing characterized by renewed flinching beginning 15 min after injury and lasting 40 min or more (phase 2). In previous work, isoflurane, administered during phase 1, slightly reduced phase-2 activity, whereas the addition of intrathecal morphine dramatically inhibited phase 2, even with naloxone reversal 6 min after the formalin injection. We used a similar model to determine whether intrathecal morphine could block spinal sensitization in the absence of inhalation anesthetic. METHODS: Hot plate tests at 52 degrees C and radiant heat-evoked hindpaw withdrawal tests were used to determine optimal doses of agonists and antagonists. The formalin test was carried out on male Sprague-Dawley rats, which were divided into five groups. A combination of naloxone 0.5 mg/kg and naltrexone 0.5 mg/kg was administered subcutaneously 6 min after the formalin injection to all animals except controls (group 1) to prevent ongoing opioid effect. Groups 1-3 received intrathecal saline, and groups 4 and 5 received intrathecal morphine 30 micrograms 20 min before formalin injection. Halothane was administered for 1-2 min to facilitate formalin injection for groups 1, 2, and 4. In groups 3 and 5 halothane was administered from 5 min before to 6 min after formalin injection. The number of flinches per minute was counted 1 and 5 min after formalin administration and thereafter at 5-min intervals for 1 h. The total number of flinches at 1 and 5 min was considered as phase-1 activity, and the total number of flinches during the 10-60-min interval was considered as phase 2. RESULTS: Phase-2 activity for groups 1 and 2 was nearly identical, demonstrating no appreciable effect of the opioid antagonists alone. Groups 3 (halothane alone) and 4 (morphine alone) exhibited a significant decrease in phase-2 activity. Group 5 (morphine plus halothane) demonstrated a profound decrease in phase-2 activity, which was significantly more profound than that of groups 3 or 4. CONCLUSIONS: Intrathecal morphine, administered before formalin injection but antagonized before the onset of phase 2 of the formalin test, significantly suppresses sensitization of dorsal horn neurons. This suppression is significantly increased by coadministration of halothane anesthesia.
Animals↗
Factors associated with failure of trigger point injections.
OBJECTIVE: The purpose of this study was to investigate factors that may influence the outcome of trigger point injections for myofascial pain syndrome. No prior studies have correlated preexisting factors with treatment outcome or assessed the magnitude of risk of treatment failure associated with such factors. DESIGN AND PATIENTS: Thirty-one factors derived from patient evaluation and physical examination were selected according to prior studies of mixed pain groups focusing on clinical importance and ease of assessment in a typical clinic setting. Included in the analysis were 193 patients who received trigger point injections and who completed baseline questionnaires. Factors were analyzed via univariate and logistic regression analyses both for independent association with short-term treatment outcome and for magnitude of risk of failure associated with each factor following adjustment for other factors. RESULTS: In univariate analysis an increased risk of treatment failure was associated with unemployment due to pain at the start of treatment, no relief from analgesic medication, constant pain, high levels of pain-at-its-worst and pain-at-its least, prolonged duration of pain, change in social activity, and lower levels of coping ability. Alcohol use was associated with a decreased risk of treatment failure. In logistic regression analysis, only lack of employment, prolonged duration, and change in social activity were independently associated with treatment outcome. Constant-versus-intermittent pain was included in the logistic model because there was an increase in risk that may be clinically important and because it influenced the effect of change in social activity. These results were not affected by the number or type of additional treatments the patients had. CONCLUSIONS: These results suggest that several factors should be considered in treating myofascial pain patients with trigger point injections, and this study supports the belief that pain is a multidimensional problem and that a variety of factors may influence treatment outcome.
Adult↗
Systemic lidocaine blocks nerve injury-induced hyperalgesia and nociceptor-driven spinal sensitization in the rat.
BACKGROUND: Repetitive C-fiber stimulation induces a state of facilitated processing of sensory information in the dorsal horn, while chronic nerve compression gives rise to a hyperalgesic state, characterized by spontaneous neuronal activity generated by voltage-sensitive sodium channels, as well as spinal facilitation. This study investigates the effects of systemic local anesthetic on thermal hyperalgesia evoked by chronic nerve compression and on the pain behavior responses to subcutaneous formalin. METHODS: The effects of intravenous lidocaine were evaluated in rats with (1) the formalin test, a model of acute pain and centrally mediated delayed sensory sensitization, and (2) a model of chronic sciatic nerve compression leading to a neurogenic thermal hyperalgesia. Groups of rats (300 g) undergoing formalin testing were given intravenous lidocaine in doses of: 3 mg plus 25 micrograms/min infusion (yielding serum levels of 6.3 +/- 1.0 micrograms/ml) or 1.5 mg plus 12.5 micrograms/min infusion (yielding serum levels of 3.6 +/- 0.3 micrograms/ml) beginning 5 min before the subcutaneous injection of formalin in the left hind paw. In other studies, a group of six animals were rendered hyperalgesic in one hind limb by the placement of compressive ligatures about the left sciatic nerve (Bennett model) 3-5 days before these studies. These rats were treated with 0.6 mg intravenous lidocaine followed by an infusion of lidocaine at a rate of 5 micrograms/min (yielding serum levels of 1.0 +/- 0.1 micrograms/ml). RESULTS: Lidocaine had no significant effect on the first phase of the formalin test or on thermal response latencies in normal limbs. However, at a high dose, lidocaine significantly reduced phase 2 flinching behavior and at a low dose, reversed the thermal hyperalgesia produced by sciatic nerve ligation during 30 min of infusion for a period of 3 h after the infusion was discontinued. CONCLUSIONS: Intravenous lidocaine acts by distinct mechanisms to diminish the hyperesthetic state induced by peripheral nerve injury and to reduce the degree of spinal sensitization induced by C-afferent fiber activation.
Animals↗
Psychoactive substance use among American anesthesiologists: a 30-year retrospective study.
The purpose of this study was to assess the cumulative incidence of substance use among anesthesiologists during training and practice, the effect of stress on drug use, and deterrent efficacy of institutional prevention programmes. The 260 anesthesiologists who had trained at the Medical College of Wisconsin between 1958-1988 were surveyed by mail regarding psychoactive substance use. Analysis of 183 responses focused on demographic and psychosocial factors. Substances used most frequently included: alcohol (91.6%), marijuana (30.8%) and cocaine (9.4%). Twenty-nine (15.8%) anesthesiologists were identified as being substance-dependent: 19 were alcohol-impaired; six were drug-impaired, and four were dependent on both alcohol and drugs. Impairment was more prevalent in anesthesiologists who had completed their training after 1975. Fifty-eight (32%) anesthesiologists had used illicit drugs to "get high"; 11 acknowledged daily use for two weeks or more, with eight admitting dependency. Substance abuse was more common in parents of impaired anesthesiologists (35.7%) than in unimpaired colleagues (8.1%; P < 0.001). The divorce rate for impaired anesthesiologists (24.1%) was greater than for unimpaired anesthesiologists (5.2%; P < 0.001). Increased stress during training was not reflected by increased substance use. Few recalled any drug counseling whatsoever. Seventy percent assessed hospital drug control policies as fair or poor. Younger respondents (born after 1951) were more critical of drug control programmes than their older cohort. Incidents of substance abuse were reported for both residents and faculty. Psychoactive substance abuse remains a serious problem among anesthesiologists.
Adult↗