Stephen E. Abram

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 alpha2-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. (Anesth Analg 1995;81:501-7)

Increased skin temperature during transcutaneous electrical stimulation.

Conflicting reports have appeared in the literature concerning the effects of transcutaneous electrical nerve stimulation on skin temperature. This report studied 33 patients with chronic pain involving one extremity (13 upper, 20 lower) to determine whether changes in sympathetic tone, as reflected in skin temperature, occurred in response to electrical stimulation of painful areas. Stimulation was carried out for 20 to 45 minutes. Skin temperatures were measured from the thumbs or great toes of stimulated and contralateral extremities before and during stimulation. Skin temperature rose 2.5 ± 0.7 C (mean ± SEM) in both the ipsilateral and contralateral extremity in patients who experienced relief of pain during stimulation. There was no significant change in skin temperature in patients who experienced no relief.

Failure of Naloxone to Reverse Analgesia from Transcutaneous Electrical Stimulation in Patients with Chronic Pain

To investigate the possible role of endogenous opiates in the mediation of analgesia produced by low intensity, high frequency transcutaneous electrical stimulation in the presence of chronic pain, an attempt was made to reverse stimulation-induced analgesia with naloxone. Fifteen patients with chronic pain who were consistently relieved of pain by low intensity, high frequency transcutaneous stimulation were studied. During stimulation at 58 Hz, patients were given double-blind intravenous injections of either naloxone (0.4 or 1.2 mg) or saline. Subjective pain ratings were recorded before stimulation, after Stimulation, and after naloxone and saline injections. No reversal of analgesia was seen after naloxone or saline. These results suggest that transcutaneous stimulation at low intensity and high frequency may provide analgesia that is not associated with release of endogenous opiates in patients with chronic pain.

Pain mechanisms in lumbar radiculopathy.

Xavier et al (1) have reported a series of patients with symptoms of lumbar radiculopathy who experit,nced days to weeks of pain relief following sciatic nerve block. A decade ago their results would have been seriously questioned, as they would have contradicted the current pathophysiological theories of the origin of pain associated with nerve root compression. Today, their findings are surprising, but not mvstifying, since recent neurophysiological studies have provided us with some reasonable explanations of this phenomenon. There has been a slow evolution of our understanding of the mechanism of the pain induccd by disc herniation and radiculopathy. In 1934, Mixter and Barr (2) demonstrated a relationship between intervertebral disc herniation and sciatica. Thcir report heralded a long era of surgical management of sciatica. It seemed obvious that disc protrusion caused nerve root compression and that compression caused pain. Surgical removal of the disc should, ostensibly, relieve the pain. Unfortunately, this simple solution has not always proven effective. Hirsch and Nachemson (3) found that only 11% of 232 patients with sciatica were pain-free 2 years ifter surgery. Other studies report almost identical results. There must, tlierefore, be a more complex explanation of the pathophysiology of sciatica. I n 1977 Murphy (4) published a rather extensive treatise, based largely on anatomic studies, on the development of lumbar radiculopathy. He proposed that the herniated disc produces nerve root injury by either mechanical compression or chemical injury caused by substances released from the degenerating

Differential Neural Effects of Epidural Anesthetics

The purpose of this investigation was to clarify in a laboratory model the sites of action of epidurally administered local anesthetics. This report describes such a model, which is capable of monitoring sites of altered electrophysiologic activity induced by epidural anesthetic agents. Evoked potential response alterations measured from electrodes positioned along the conducting pathways were assessed in six monkeys following epidural injections of 0.5 per cent bupivacaine, 3 per cent chloroprocaine, and 1 per cent etidocaine. Bupivacaine in ten studies was found to cause its major effects at the dorsal root entry zone and the long tracts of the spinal cord white matter, associated with variable peripheral nerve alterations. Chloroprocaine effects in six studies were limited to alteration of responses recorded from the dorsal root entry zone and peripheral nerve. In contrast, etidocaine in eight studies caused marked attenuation of the responses recorded from the long tracts of the spinal cord white matter, associated with only minimal corresponding changes at the dorsal entry zone or peripheral nerve levels. These findings illustrate the capability of this experimental model to demonstrate relatively selective effects along the sensory and motor pathways for epidurally injected local anesthetic agents.

Subarachnoid Corticosteroid Injection Following Inadequate Response to Epidural Steroids for Sciatica

A review of pain clinic patients was carried out to determine whether patients who obtained limited or no relief from epidural injection of steroids derived benefit from subsequent subarachnoid steroid injections. Only 1 of 13 patients who had no benefit from epidural steroids improved following subarachnoid injection. Five of 6 patients with partial relief from epidural steroids had further improvement after subarachnoid injection.

Altered neural conduction with epidural bupivacaine.

The sites and magnitude of evoked potential response alterations induced by varying masses and concentrations of epidurally administered bupivacaine were assessed from electrodes positioned along the conducting pathways of the monkey. The mass of bupivacaine was the major factor in determining the level and degree of response alterations. At the lower levels of total drug mass, effects were limited to the dorsal root entry zone, whereas higher levels of mass not only increased the response attenuation at the gray matter level but resulted in additional changes in those responses recorded from the spinal cord white matter tracts. With all other factors stable, increasing concentration was associated with a greater degree of response attenuation, especially at the lower levels of total mass. These findings indicate that the mass of the drug is the major factor in determining the magnitude and level of bupivacaine-induced epidural analgesia. Increased concentration influences the local anesthetics penetration at the dorsal root entry zone and, to a lesser degree, at the white tracts of the spinal cord.

Continuous epidural analgesia for cesarean section in a patient with morbid obesity.

A 20-year-old white woman, gravida 3 para 1, 177 cm tall and weighing more than 182 kg (scale not readable over 400 pounds), was admitted for an elective repeat cesarean section. Past medical history included chronic hypertension with blood pressure in the range of 160/110 torr. During her pregnancy she was treated with phenobarbital, 15 mg, 4 times a day. Past history included two general anesthetics, one for her primary cesarean section and one for uterine dilation and curettage. She denied shortness of breath or periodic somnolence. Laboratory data were within normal limits. Preoperative medication consisted of oral antacid 45 minutes prior to induction. With an 18-cm thigh cuff applied to her arm, pre-anesthetic blood pressures in the range of 115