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Biomedical subjects

M J Cousins

Publications and source records attributed to M J Cousins.

At least 37 records · Page 2Linked to original sources

The long-term effect of epidural administration of butamben suspension on nerve injury-induced allodynia in rats.

UNLABELLED: Although local anesthetics can, in some situations, alleviate neuropathic pain, currently available preparations are short-acting and nonselective, producing, for example, motor dysfunction. Clinical studies report that a novel suspension preparation of butamben has the advantage of a prolonged duration of action, and it can be used epidurally, without impairment of motor function. In this behavioral study, we investigated the effect of the epidural administration of a 5% butamben suspension on nerve injury-induced allodynia. Behavioral studies were performed using an established animal model of neuropathic pain, which involves a partial ligation of the sciatic nerve. Nociceptive thresholds to mechanical stimulation were determined by the paw withdrawal method. The allodynia to mechanical stimulation induced by partial nerve ligation was significantly attenuated by daily injections, for 5 days, of 10 microL of butamben suspension. The analgesia lasted at least 7 days after the final injection. Daily injections of 10 microL of vehicle, for 5 days, had no significant effect on allodynia. During the period of daily injections, both the butamben and vehicle treated rats had temporary impairment of motor coordination compared with untreated controls. Motor function recovered after the final injection. Neither daily injections of butamben for 2 or 3 days, nor smaller volumes for 5 days (2.5-5 microL), had a long-lasting effect. We conclude that repeated epidural administration of butamben suspension for several days provides long-lasting analgesia in rats with nerve injury-induced allodynia to mechanical stimulation. IMPLICATIONS: In this animal behavioral study, using rats with nerve injury-induced pain, we examined the possible long-term analgesic effects of epidural administration of a suspension of the local anesthetic, butamben. We found that multiple doses for several days were required to provide a prolonged analgesia.

Analgesia, Epidural↗

Renal dysfunction associated with the perioperative use of diclofenac.

UNLABELLED: Postoperative renal dysfunction in rats is induced by ketorolac dosed concurrently with gentamicin. Herein, we report the renal effects of diclofenac in four groups of rats: control (C = anesthesia, surgery); diclofenac (D = anesthesia, surgery, diclofenac 18 mg x kg(-1) x d(-1)); gentamicin (G = anesthesia, surgery, gentamicin 20 mg x kg(-1) x d(-1)); and diclofenac and gentamicin (DG = anesthesia, surgery, diclofenac, gentamicin). Renal function, after three treatment days, was assessed using histology, p-aminohippurate (PAH), and iothalamate (IOT) clearances, serum and urine electrolytes, osmolality, urea, and creatinine. Urine output was increased (from 5.2 to 12.5 mL/24 h), and urine osmolality was decreased (from 2121 to 883 mOsm/kg) in the DG group. PAH and IOT clearances were decreased in the G and DG groups (PAH by 18%, IOT by 22%; PAH by 38%, IOT by 43%, respectively); there were no changes in the C and D groups. Urea and creatinine clearances were decreased by 61% and 43%, respectively, in the DG group. Kidney sections showed the most severe pathologic changes in the DG group. Our data indicate that the perioperative combination of diclofenac and gentamicin was deleterious to renal function. IMPLICATIONS: Diclofenac alone does not result in significant perioperative renal dysfunction, but the combination of gentamicin and diclofenac is deleterious to renal function. Considering this and previous findings, the evidence suggests that treatment with aminoglycosides may be a significant risk factor for inducing perioperative renal failure during treatment with nonsteroidal antiinflammatory drugs.

Animals↗

Toward a canon of the pain and analgesia literature: a citation analysis.

UNLABELLED: The purpose of this study was to use citation analysis to identify major themes and contributors to the pain and analgesia literature over the past two decades. A citation analysis was performed on a database of more than 110,000 articles in the biomedical literature from January 1981 through June 1997, and in the interval from January 1988 through June 1997. Articles and authors related to pain and analgesia research and practice were identified by searching approximately 7,700 journals. The 20 articles and 20 authors with the most citations were then checked by hand to ensure relevance to pain or analgesia. Most of the high-impact articles identified pertained to research on basic pain pathways. Nearly all the articles concerned opioids, nonsteroidal antiinflammatory drugs, and consequences of analgesic use. None of the highest-impact articles address assessment of clinical pain. Few women were first authors of any most frequently cited paper. Citation analysis is a useful tool in identifying important contributions to the biomedical literature. Recent and continuing research trends include the use of nonsteroidal antiinflammatory drugs, opioid mechanisms, and persistent pain disorders. Current trends expected to become stronger include description of pain from the patient's perspective and mechanisms of the transition from acute to chronic pain. IMPLICATIONS: We performed a citation analysis to identify important contributions and contributors to the biomedical literature. Recent pain and analgesia research has been focused on mechanisms of pain, but evidence suggests the importance of understanding the pain experience from the patient's perspective and the transition from acute to chronic pain.

Analgesia↗

Epidural analgesia reduces the release of amino acids from peripheral tissues in the ebb phase of the metabolic response to major upper abdominal surgery.

The purpose of this prospective cohort study was to compare metabolic effects of epidural or patient controlled analgesia (PCA) in patients undergoing major upper abdominal surgery. Seventeen patients undergoing major upper abdominal surgery were included: 10 received perioperative epidural analgesia (Group I) and the remainder received morphine via a PCA device for postoperative analgesia (Group II). A number of measures compared between one day preoperatively (day 1) and day 2 postoperatively included femoral arterial and venous blood concentrations of glucose, lactate, pyruvate and amino acids. In addition, the relevant flux values were measured from the products of the respective arteriovenous substrate concentration differences and calf blood flow. The efflux of lactate from peripheral tissues was greater in Group II than in Group I (P < 0.01): glucose and pyruvate efflux did not differ between groups. There was no difference between groups in mean individual and total flux of amino acids on day-1. However increased efflux between day-1 and day 2 was found for alanine, valine, isoleucine, leucine, phenylalanine, lysine, arginine in both groups, and for serine, glycine, tyrosine and histidine in Group II (P < 0.05). The efflux of glycine, methionine, amino benzoic acid, alanine, and lysine was less in Group I than Group II on day 2 (P < 0.05). There was a significant difference in the total amino acid flux on day 2 (Group I = -1.2 mumol. (100 ml tissue)-1.min-1 cf Group II = -2.5 mumol. (100 ml tissue)-1.min-1; P = 0.04). In conclusion, perioperative epidural analgesia was associated with a reduced postoperative amino acid efflux two days following major upper abdominal surgery.

Amino Acids↗

Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia.

Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.

Afferent Pathways↗

Analysis of 50 patients with atypical odontalgia. A preliminary report on pharmacological procedures for diagnosis and treatment.

Atypical odontalgia is a distressing and unusual chronic orofacial pain condition. It is often difficult to diagnose because it is associated with a lack of clinical and radiographic abnormalities. The condition is poorly understood on a pathophysiological basis, and patients often undergo repetitive and unnecessary dental procedures in attempts to alleviate pain. In this study, 50 patients diagnosed with odontalgia were evaluated by pharmacological procedures, including topical anesthetic application and phentolamine infusion. Results of these pharmacological procedures suggest that atypical odontalgia is a neuropathic pain of the oral cavity that may have a component of sympathetically maintained pain. Therapeutic trials of topical capsaicin were carried out to assess its efficacy for pain reduction. Topical capsaicin was effective in most patients.

Administration, Topical↗

Factors influencing ketorolac-associated perioperative renal dysfunction.

UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of postoperative pain, but there is continuing concern about adverse effects on renal function. We studied the renal effects of ketorolac in an animal model using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1)) (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals. Renal function was assessed before laparotomy and after 3 treatment days using concurrent paraaminohippurate and iothalamate clearances, respectively, to estimate renal plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significant increase in serum potassium was found in the GK and DK groups. There were no major changes in renal function in the C, K, KH, and DK groups. Mild renal dysfunction was found in the G group. We found severe and consistent changes in renal function, accompanied by severe, widespread histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentamicin was deleterious to renal function. IMPLICATIONS: We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ketorolac plus the antibiotic gentamicin produced marked changes in kidney function and structure.

Animals↗

Pain description and severity of chronic orofacial pain conditions.

A multidisciplinary pain centre study of 120 consecutive chronic orofacial pain patients assessed pain description and intensity ratings, gender differences, prevalence of concurrent conditions, and interinstrument relationships of the McGill Pain Questionnaire and visual analogue scale. Pain words chosen by patients to describe conditions were predominantly sensory words, and patients with concurrent conditions often listed words indicating a substantial affective component. Results showed pain intensity ratings of chronic orofacial pain conditions have similar or higher pain ratings when compared with other medical chronic pain conditions such as back pain, cancer pain and arthritis. There was a significantly higher female: male ratio (88:32) with gender playing an important but poorly understood causal role. The most frequent condition diagnosed was atypical facial pain (n = 40), followed by temporomandibular disorder (n = 32), atypical odontalgia (n = 29) and pathology of the orofacial region (n = 19). Temporomandibular disorder was present in 75 of the 120 subjects, as the sole pain complaint (n = 32) or as an associated secondary condition (n = 43), indicating concurrent pain conditions exist and may be related. There were significantly higher total pain scores of the McGill Pain Questionnaire in patients with multiple conditions compared with patients with a single condition. The visual analogue scale showed a significant correlation to the number of words chosen index of the McGill Pain Questionnaire for orofacial pain.

Adolescent↗

Propofol maintenance to reduce postoperative emesis in thyroidectomy patients: a group sequential comparison with isoflurane/nitrous oxide.

The clinical benefit of propofol anaesthesia in the prevention of postoperative nausea and vomiting (PONV) is still being elucidated despite many studies to date. In this study 64 adult female patients scheduled for thyroidectomy received, in a randomized double-blind fashion, propofol with air or isoflurane with nitrous oxide for maintenance of anaesthesia. The primary response variable was the presence or absence of vomiting in the first six hours. A group sequential design was used to allow interim analysis. After 64 patients, the fourth analysis showed that fewer patients receiving propofol vomited or required an anti-emetic during the first six hours (P < 0.05). There was no significant difference detected in the 6 to 24 hour interval. In this group of female patients, total intravenous anaesthesia (TIVA) with propofol is associated with an early reduction in early postoperative vomiting compared with standard inhalational techniques. This reduction in vomiting does not appear to persist beyond the first six hours.

Adult↗

Preoperative dextromethorphan reduces intraoperative but not postoperative morphine requirements after laparotomy.

UNLABELLED: N-methyl-D-aspartate (NMDA) antagonists combined with opioids are thought to be effective in the control of pain states. We evaluated morphine use and analgesia in 37 patients postlaparotomy. Patients received 60 mg of oral dextromethorphan or placebo the night before and again 1 h before surgery. Morphine was titrated intraoperatively to maintain blood pressure and heart rate within 20% of baseline and postoperatively via patient-controlled analgesia (PCA). The dextromethorphan and placebo groups were compared for morphine use intraoperatively, in recovery, via PCA in the first 4 and 24 h, and total use over the study period. Pain scores at rest and on activity for the first 4 and 24 h were also compared. Intraoperatively, the dextromethorphan group required less morphine: 13.1+/-4.3 vs 17.6+/-6.0 mg (P = 0.012). Postoperatively, there was no significant difference between the dextromethorphan and placebo groups for morphine use: in the recovery room 10.9+/-7.7 vs 12.1+/-7.7 mg; the first 4 h of PCA 15.9+/-9.3 vs 12.7+/-5.1 mg; the first 24 h of PCA 76.4+/-44.7 vs 61.8+/-27.5 mg; or in total morphine use 100.4+/-49.5 vs 91.5+/-3.1 mg. Pain scores for the two groups were not statistically different throughout the study period. We conclude that 60 mg of oral dextromethorphan given the night before and repeated an hour before surgery does not provide a postoperative morphine-sparing effect or improve analgesia after laparotomy. IMPLICATIONS: Patients given dextromethorphan before surgery had significantly reduced intraoperative morphine requirements. However, postoperative morphine requirements were unaltered. Dextromethorphan may need to be continued postoperatively to improve postoperative analgesia.

Abdomen↗

Spinal pain mechanisms.

Pain is an extremely complex process that involves the interaction of an array of neurotransmitters and neuromodulators at all levels of the neuraxis. Identification of the receptors and processes that are involved in the transmission of pain at a spinal level has led to the use of new agents and new techniques in pain management. These include use of preemptive analgesia and use of techniques such as intrathecal drug administration and epidural spinal cord stimulation. This review presents some of the findings from basic research that have led to these developments, particularly those that relate to the changes that occur following inflammation and nerve injury.

Humans↗

Classification of pain following spinal cord injury.

Pain continues to be a significant management problem in people with spinal cord injuries. Despite this there is little consensus regarding the nature, terminology and definitions of the various types of pain that occur following spinal cord injury. This has led to large variations in the reported incidence and prevalence of pain following spinal cord injury. Treatment studies have been hampered by inconsistent and inaccurate identification of pain types. We believe that both research and management would benefit from an agreed upon classification system which accurately and reliably identifies the types of pain that occur following spinal cord injury. We have reviewed the literature on the classification of pain following spinal cord injury and have developed a classification system which adopts the strengths of previous systems and attempts to avoid the weakness inherent in others. Our proposed classification system of pain following spinal cord injury includes four major divisions: musculoskeletal, visceral, neuropathic and other types of pain. We have divided neuropathic pain on the basis of region into two subdivisions: neuropathic at level and neuropathic below level pain. We have further divided neuropathic at level pain into two categories: radicular and central, to indicate the presumed site of the lesion responsible for pain generation. We believe that our proposed classification system is comprehensive, simple and readily applicable in the clinical and research situation. It is our hope that this proposed classification will contribute to the eventual development of a universal system for the classification of pain following spinal cord injury.

Humans↗

Relationship between surgery and pain following spinal cord injury.

Pain is a significant problem following spinal cord injury (SCI) and has a major influence on quality of life and the ability to engage in rehabilitation. Surgery is often indicated in the management of spinal cord injury to stabilise the spine and prevent further neurological deficit. However, the relationship between surgical intervention and the presence of pain following SCI is unclear. We performed a prospective, longitudinal study of 100 individuals with traumatic SCI to determine the prevalence of different types of SCI pain at 2, 4, 8, 13, 26 and 52 weeks following SCI and to determine whether there was a relationship between surgical intervention and the presence or absence of specific types of SCI pain. We found that surgical intervention was associated with a significantly higher prevalence of musculoskeletal pain at 2 weeks but not at 4, 8, 13, 26 and 52 weeks following injury, when compared with those who did not have surgery. There were no significant differences in the prevalence of visceral, neuropathic at level or neuropathic below level pain in the surgical and non-surgical groups at any stage. The results from this study suggest that apart from an increased prevalence of musculoskeletal pain at 2 weeks following SCI in those who undergo surgery, there is no significant relationship between surgical intervention and the presence of SCI pain.

Follow-Up Studies↗

Neural blockade in chronic and cancer pain.

Neural blockade can provide significant pain relief to patients with chronic and cancer pain but must be used in the correct manner and only on selected patients. The hazards of performing neurolytic treatments have become apparent with time and demonstrate the need to examine the long-term outcomes of these procedures. The present challenge is to identify with controlled trials those patients with chronic pain who would benefit from neural blockade.

Chronic Disease↗