Evidence-based surgery: time for change.
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Animals↗
Biomedical subjects
Dorothy C Brown
Publications and source records attributed to Dorothy C Brown.
Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control.
Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management.
Adult↗
Use of noninvasive dental dolorimetry to evaluate analgesic effects of intravenous and intrathecal administration of morphine in anesthetized dogs.
OBJECTIVE: To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine. ANIMALS: 6 male Beagles that were 2 to 6 years old. PROCEDURE: Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination. RESULTS: The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle.
Analgesics, Opioid↗
Effect of intrathecal and intravenous administration of oxytocin on amplitude of the reflex-evoked muscle action potential after electrical stimulation of the tooth pulp in anesthetized dogs.
OBJECTIVE: To determine whether intrathecal (IT) or IV administration of oxytocin will diminish amplitude of the reflex-evoked muscle action potential (REMP) in the digastricus muscle during electrical stimulation of the tooth pulp in anesthetized dogs, thus suggesting an analgesic effect for oxytocin. ANIMALS: 6 male Beagles that were 2 to 6 years old. PROCEDURE: Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin by both the IT and IV routes of administration. Noninvasive dental dolorimetry was used to assess changes in pain threshold following administration of treatments. Effectiveness of analgesia was determined on the basis of change in REMP amplitude in the digastricus muscle. RESULTS: Morphine administered IV significantly inhibited REMP amplitude, compared with IV administration of saline solution or oxytocin. There was not a significant change in REMP amplitude between saline solution and oxytocin administered IV. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution or oxytocin. Intrathecal administration of oxytocin significantly increased REMP amplitude, compared with IT administration of saline solution or morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Although IV administration of oxytocin did not have an effect on REMP amplitude, compared with IV administration of saline solution, IT administration of oxytocin had the opposite effect of morphine and increased REMP amplitude of the digastricus muscle. These data do not support the use of oxytocin as an analgesic agent in dogs.
Action Potentials↗
Prognostic indicators for time to ambulation after surgical decompression in nonambulatory dogs with acute thoracolumbar disk extrusions: 112 cases.
OBJECTIVES: To determine prognostic indicators for time to ambulation after surgical decompression in nonambulatory dogs with intact pain sensation and acute Hansen type-1 disk extrusions. STUDY DESIGN: Retrospective clinical study. ANIMALS: One-hundred twelve dogs with Hansen type-I disk extrusions that had decompressive hemilaminectomy or dorsal laminectomy. METHODS: All dogs had thoracolumbar disk extrusion and were nonambulatory with intact pain sensation at admission. Variables considered included age, weight, voluntary motor function at time of anesthetic induction, glucocorticoid use, times from onset of nonambulatory status to admission and surgical decompression, time in hospital to surgical decompression, anesthetic time, surgical time, number of contrast injections required to perform a diagnostic myelogram, postoperative pain sensation, and postoperative voluntary motor function. Time to ambulation was defined as the number of days from surgical decompression until the dog was able to stand and take a series of steps without assistance. RESULTS: One-hundred seven dogs (96%) were able to ambulate within 3 months. The mean time to ambulation was 12.9 days and was significantly shorter if dogs had postoperative voluntary motor function (7.9 days v 16.4 days, P <.0001). No other variable had a significant association with time to ambulation. CONCLUSIONS: Few perioperative variables have prognostic value for return to ambulation. Nonambulatory dogs with intact pain sensation and Hansen type-1 disk extrusions in the thoracolumbar spine that are treated with surgical decompression have a favorable prognosis. CLINICAL RELEVANCE: The presence of postoperative voluntary motor function is a favorable prognostic indicator for early return to ambulation.
Acute Disease↗