Maintain Pain Control Research Articles

Effects of botulinum toxin type A on the superior cervical ganglia in rabbits

Sympathetic neurolysis is very important in treating chronic pain, especially sympathetically maintained pain. However, conventional neurolytic agents destroy nerve fibers nonselectively and may leave serious complications. Botulinum toxin type A (BTA) selectively acts on cholinergic nerves and inhibits the secretion of acetylcholines (Ach) at the involved nerve endings. Because cholinergic nerves also exist in autonomic ganglia, it is believed that BTA has pharmacological effects on sympathetic ganglia. In this study, after the administration of BTA into the superior cervical ganglion (SCG) in rabbits, the possible clinical use of BTA as a neurolytic agent was evaluated. In the normal saline-treated control group, miosis was not observed in all 12 rabbits. However, in the BTA-treated group, 15 cases of miosis were observed among 40 rabbits (37.5%). Furthermore, BTA induced miosis in a dose-dependent manner, though onset time and duration of miosis varied. Mean time of onset and duration were 1.8 days and 5.3 weeks, respectively. By eosin–hematoxylin (H&E) staining finding, no significant chronological and histological changes between the control and the experimental groups were observed. In conclusion, BTA was found to have a sympathetic ganglion blocking effect over a period of more than 1 month without causing considerable pathologic changes in the SCG, that is, this toxin may be used in the case of sympathetically maintained pain control as a sympatholytic.

New directions in pain management.

Pain medicine is one of the most rapidly developing medical specialties of today. While there are many modalities that can be used in managing the patient in pain, drug treatment remains, for the most part, the cornerstone of treatment. Opioids retain their position as the foundation of most analgesic strategies, although they tend to be used nowadays in combination with adjuvant analgesics such as paracetamol and nonsteroidal antiinflammatory drugs. The range of available opioids has also been expanded with drugs such as hydromorphone and oxycodone, originally developed almost a century ago. This expanded choice has resulted in the concept of opioid rotation in chronic pain states, an approach that is aimed at maintaining pain control while minimizing adverse effects. Nonsteroidal antiinflammatory drugs continue to play an important role, especially as adjuvants, and the development of drugs such as celecoxib and refecoxib, highly specific for the inhibition of cyclooxygenase 2 pathway has been a further advance. The treatment of neuropathic pain continues to be a challenge to the clinician. While this has traditionally been treated with drugs from the anticonvulsant, antiarrhythmic and anti-depressant groups, results from these treatments have often been less than satisfactory. This has led to the development of completely new drug classes that modulate neuronal transmission in pain pathways, some of which are derived from exotic animal sources, such as the conotoxins from the marine snail family and epibatidine from a species of frog. The role of cannabinoids remains controversial.

Low-Dose Oral Naloxone Reverses Opioid-Induced Constipation and Analgesia

The most common side effect of opioid therapy is constipation. It is often difficult to treat and is believed to be primarily a peripheral effect. Single large doses of oral naloxone have been shown to be efficacious in reversing opioid-induced constipation. However, they often cause the unwanted side effect of analgesia reversal. This study evaluated the effects on constipation and analgesia of low doses of oral naloxone given three times daily. Patients taking stable doses of opioids with complaints of constipation were recruited for this double-blind, randomized, placebo-controlled study. Patients were given 4 mg or 2 mg of oral naloxone, or placebo, three times daily. Stool frequency and symptoms related to constipation were recorded daily. Patients also recorded the daily amount of analgesics required to maintain pain control. Nine patients were recruited for the study. All the patients who received oral naloxone had some improvement in their bowel frequency. Three of the patients also experienced reversal of analgesia, including one who had complete reversal of analgesia. This study demonstrates that reversal of analgesia still occurred despite dividing the oral naloxone into very low doses relative to the total dose of opioid used. Patients using high doses of opioids appear to be the most vulnerable to the antalgesic effect of oral naloxone.

(205) Steady-State Pharmacokinetic Comparison of MorphelanR ROERR (Morphine Sulfate Rapid Onset Extended Release) Once-a-Day and Morphine Oral Solution Administered Q4H around-the-Clock in Healthy Volunteers

Introduction: Controlled-release morphine formulations have been developed to decrease the dosing frequency needed to maintain pain control around-the-clock (ATC). Morphelan® ROER® (MROER), a novel, once-a-day, rapid onset extended release morphine formulation, was designed to rapidly reach target concentrations and to maintain therapeutic concentrations throughout a 24-hour dosing interval. Objective: To compare 24-hour steady-state pharmacokinetic profiles of morphine following MROER once-daily and morphine oral solution (MOS) administered q4h ATC. Methods: In an open-label, cross-over study, 12 healthy volunteers were randomized to MROER 60 mg once-daily or 10 mg q4h ATC MOS for 5 days with at least a 7-day washout before cross-over. Twenty-four-hour pharmacokinetic profiles were obtained on the last day of each study treatment. Results: Once-daily MROER rapidly releases morphine, providing plasma morphine concentrations at 30 minutes (C30min) similar to MOS following administration. Maximum concentrations (Cmax), total systemic exposure (AUC0-24h), peak-to-trough fluctuations (%FI) and plasma concentrations at 24 h (C24h) were similar between MROER once-a-day and MOS dosed q4h ATC over a 24 hour dosing interval (Table 1). Data are presented as mean ± SD. No statistical differences were observed (p < 0.05). # FL: Number of daily peak-to-trough fluctuations. Conclusions: MROER once-a-day rapidly reaches target plasma morphine concentrations and maintains similar therapeutic concentrations as MOS dosed q4h ATC over a 24-hour dosing interval with fewer peak-to-trough fluctuations. Therefore, MROER represents a true once-a-day controlled-release morphine formulation. Table 1. Parameter MROER (once-a-day) MOS (q4h ATC) AUC0-24h (ng×h /ml) 273 ± 81.2 279 ± 63.0 Cmax (ng/ml) 18.7 ± 7.13 20.0 ± 4.82 C30min (ng/ml) 12.9 ± 6.64 15.0 ± 4.05 C24h (ng/ml) 7.84 ± 2.99 9.45 ± 2.81 %FI 106 ± 78.1 116 ± 26.7 # FL 1 6

Thoughts and feelings of in-patients with advanced terminal cancer: implications for terminal care improvement.

The purpose of this study was to clarify how terminally ill patients think and feel while hospitalized, thereby providing some insight into improving the quality of terminal care. The subjects of the study were eight terminally ill patients with cancer. The researchers obtained the patients' consent and their doctors' permission prior to conducting the interviews. Individual, semi-structured interviews were conducted. The patients' thoughts and feelings were extracted and then categorized according to particular themes. As a result, we came up with four major categories: maintaining pain control, living an ordinary life, hoping for improvement of physical condition, and having family nearby. The desire to live life to its fullest given their situation, as well as to maintain a hopeful attitude about their future proved very important. The presence of family also played a crucial role. These factors must be taken into consideration in achieving better care for terminally ill patients.

Effectiveness of bupivacaine administered via femoral nerve catheter for pain control after anterior cruciate ligament repair

Study Objective: To evaluate the quality of pain control achieved with continuous local anesthetic infusion via a femoral nerve catheter, and to determine the optimum concentration of bupivacaine necessary to maintain pain control after full surgical anesthesia is established with 0.5% bupivacaine. Design: Randomized, prospective study. Setting: Tertiary care teaching center. Patients: 25 ASA physical status I and II patients scheduled to undergo arthroscopically-aided anterior cruciate ligament (ACL) reconstruction by one surgeon, and who were willing to accept a femoral nerve catheter for postoperative pain control. Interventions: All patients received general anesthesia with propofol/alfentanil (10 ml/1 ml) mixture and nitrous oxide/oxygen ( 60% 40% ) mixture via endotracheal tube. After induction of general anesthesia, a femoral nerve catheter was inserted with the aid of a nerve stimulator, and 20 ml of 0.5% bupivacaine was administered. The surgery was completed in a standard manner and the patients were randomized into three groups for the concentration of local anesthetic to continue the pain relief into the recovery phase. On awakening, all patients were determined to have a functioning femoral nerve catheter. Group 1 received 0.0625% (n = 8) bupivacaine, Group 2 0.125% (n = 9) bupivacaine, and Group 3 0.25% (n = 8) bupivacaine; all doses were initiated in a blinded manner at 0.12 ml/kg/hr. Patients also received intravenous patient-controlled analgesia with morphine via demand mode only, with a 1.0 mg dose and a 6 minute lock-out interval. Measurements and Main Results: Pain was determined at defined intervals by visual analog scale (VAS). Data collected included demographics, VAS scores, and total morphine administered. All patients were pain-free on emergence from general anesthesia. No patient required parenteral opioid for pain control while in the postanesthesia care unit. There were no significant differences in pain scores among groups, and average pain scores (2.5 to 4.0) indicate good pain control throughout the entire hospitalization. There were no complications. Conclusions: Low concentrations of bupivacaine delivered via femoral nerve catheter after an established femoral nerve block can provide excellent postoperative pain control after ACL reconstruction.

Day-to-day titration to initiate transdermal fentanyl in patients with cancer pain: Short- and long-term experiences in a prospective study of 39 patients

Initial dose finding in patients with cancer pain who are started on TTS fentanyl (Duragesic™, TTS-F) is often unsatisfactory with currently recommended doses and intervals. Acknowledging that studies reveal a “psuedo steady state” 15 to 20 hr after application of TTS-F, we prospectively investigated an increased initial dose and day-to-day titration of TTS-F in 39 (evaluable) patients with uncontrolled cancer pain. Significant pain reduction ( P = 0.001) was seen after 24 hr, and satisfactory analgesia was achieved within 48 h and maintained for the rest of the study. Significant increases in TTS-F were necessary during weeks 1 through 4 to maintain pain control. Forty-nine percent of the patients needed one or more early dose increases. Only one patient had side effects partially due to the specific properties of the TTS. Other side effects seemed to be less common compared with usual morphine treatment. TTS-F can be titrated effectively and safely on a day-to-day basis with an increased initial dose and adequate patient monitoring, thus avoiding more complicated approaches. TTS-F seemed to induce less constipation than might be expected.

Opioid rotation for toxicity reduction in terminal cancer patients

Accumulation of active (toxic) metabolites of opioids might explain cases of opioid toxicity when high doses are used for long periods of time. Other mechanisms of late toxicity of opioids may be found at the receptor level. Whatever the cause, a change of opioids using equianalgesic doses can be expected to improve symptoms of toxicity in some patients, while maintaining pain control. We reviewed the experience with this technique in patients admitted to the Palliative Care Unit of the Edmonton General Hospital. Of 191 patients, 80 underwent opioid rotation (OR) for cognitive failure, hallucinations, myoclonus, nausea and vomiting, local toxicity, and persistent pain. These leading symptoms improved in 58/80 patients (73%, P < 0.01). Pain control, as measured on a 10-cm visual analogue scale (VAS), improved from 4.4 ± 2.3 to 3.6 ± 2.0 (P < 0.004) at a dose significantly lower than that predicted to be equianalgesic (577 ± 1535 mg before OR versus 336 ± 593 mg after OR, P < 0.04). We conclude that symptoms of opioid toxicity can be relieved by OR, and that a choice of two or three different opioids is necessary to obtain satisfactory long-term pain control.

The rectal administration of MS Contin: clinical implications of use in end stage cancer.

Mercy Hospice in Nampa, Idaho administered unmodified MS Contin 30 mg tablets rectally to 39 terminally ill patients. All patients had pain controlled on oral MS Contin but were switched to the rectal route of administration because of intractable nausea, inability to swallow or both. Pain control was maintained on all patients receiving rectal MS Contin. In 11 patients, the dosage of MS Contin was decreased. No local or systemic adverse reactions developed. The rectal administration is a safe, effective and simple means of maintaining pain control in terminally ill patients.

Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain control.

Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.

Electrotherapeutic Approach to Postoperative Pain following Total Hip Replacement: A Case Study

Persistent pain following unilateral total hip replacement was approached with multiple electrical modalities. lontophoresis, with several ions for specific physiological effects, was utilized successfully. When skin irritation was encountered, high frequency sine wave, i.e., 1 kilohertz, was substituted because of its nonirritating, deep penetration qualities. Ultrasound was also utilized as an adjunct in the attempt to introduce the chemicals previously introduced by iontophoresis by way of the phonophoretic process. TENS was applied at home between office visits to maintain pain control but was not, apparently, involved in the overall rehabilitative process of the pathological conditions, since no lasting analgesic effects were noted. Traditional electrical stimulation techniques were added to the program when specific muscular weakness was noted, using surged sine wave at 1 kilohertz to the affected musculature. The favorable results of this multiphasic approach are clearly demonstrated in the relatively pain-free, functional activities of the patient. J Orthop Sports Phys Ther 1981;2(4):180-183.