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Intractable pain treated with intrathecal isotonic iced saline.

Hitchcock's original method of hypothermic subarachnoid irrigation employed both temperature and osmolarity. Spinal cooling was then abandoned in favour of intrathecal injection of normothermic hypertonic salilne. Modifications of the procedure that followed have continued to accept hyperosmolarity as the factor causing pain relief. Fifty patients were treated by a technique evolved to enhance the effect of hypothermia while avoiding the complications associated with hyperosmolar solutions. For the cases of terminal carcinoma and others considered to be poor surgical risks, the results have been quite satisfactory. For non-neoplastic painful syndromes, rapid perfusion cooling of the subarachnoid space offers an alternative therapeutic approach.

Analgesia↗

Effects of intrathecal saline and ketamine with and without preservative on the spinal nerve roots of monkeys.

Ketamine, a cataleptic analgesic substance which theoretically may block pain receptors in the spinal cord, providing pain relief without respiratory depression, was injected intrathecally with or without benzethonium chloride 0.1 mg/ml (a preservative) into 8 monkeys under anaesthesia. Two monkeys received saline (control group). No assessment as to relief from experimental pain was possible. All Monkeys recovered normally from anaesthesia and were found moving about in their enclosures without gross evidence of neurological impairment. No adverse reactions were noted. Ten days after the subarachnoid injection the monkeys are sacrificed. Autopsy was performed within 30 minutes. No macroscopic abnormality of the cord was noticed. Microscopic examination revealed oedema of a few nerve roots in all animals, irrespective of whether ketamine or saline was injected intrathecally. Focal degeneration with loss of myelin and axoplasm was observed within a solitary nerve root in 2 monkeys that had received ketamine, 1 with and 1 without preservative. However, in these animals lumbar puncture proved difficult and bloody taps ensued. Hence trauma could have been a contributing factor in these 2 cases. None of the other monkeys showed these changes, regardless of group.

Animals↗

Distribution and connections of inspiratory premotor neurons in the brainstem of the pigeon (Columba livia).

We have recorded extracellular, inspiratory-related (IR) unit activity in the medulla at locations corresponding to those of neurons retrogradely labeled by injections of retrograde tracers in the lower brachial and upper thoracic spinal cord, injections that covered cell bodies and dendrites of motoneurons innervating inspiratory muscles. Bulbospinal neurons were distributed throughout the dorsomedial and ventrolateral medulla, from the spinomedullary junction through about 0.8 mm rostral to the obex. Almost all of the 104 IR units recorded were located in corresponding parts of the ventrolateral medulla, rostral to nucleus retroambigualis, where expiratory related units are found. Injections of biotinylated dextran amine at the recording sites labeled projections both to the spinal cord and to the brainstem. In the lower brachial and upper thoracic spinal cord, bulbospinal axons traveled predominantly in the contralateral dorsolateral funiculus and terminated in close relation to the dendrites of inspiratory motoneurons retrogradely labeled with cholera toxin B-chain. In the brainstem, there were predominantly ipsilateral projections to the nucleus retroambigualis, tracheosyringeal motor nucleus (XIIts), ventrolateral nucleus of the rostral medulla, infraolivary superior nucleus, ventrolateral parabrachial nucleus, and dorsomedial nucleus of the intercollicular complex. In all these nuclei, except XIIts, retrogradely labeled neurons were also found, indicating reciprocity of the connections. These results suggest the possibility of monosynaptic connections between inspiratory premotor neurons and inspiratory motoneurons, which, together with connections of IR neurons with other brainstem respiratory-vocal nuclei, seem likely to mediate the close coordination that exists in birds between the vocal and respiratory systems. The distribution of IR neurons in birds is similar to that of the rostral ventral respiratory group (rVRG) in mammals.

Animals↗

Descending course of primary afferent collaterals in the cat's spinal cord.

After injecting horseradish-peroxidase into the lower thoracic, lumbar and sacral spinal cord segments of cats, labelled perikarya were found in several spinal ganglia localized cranially to the site of injection. The segmental distance between the injection site and the rostralmost localized ganglion with labelled cells varied depending on the medio-lateral localization of the injection. The longest distance (10 segments) was achieved by medial injections. Primary sensory neurones with long descending collaterals belong to large ganglion cells.

Animals↗

[The level of analgesia with epidural injection of 2% mepivacaine using combined spinal and epidural analgesia].

We studied the level of analgesia obtained with epidural injection of 2% mepivacaine using combined spinal and epidural analgesia (CSE) and compared with the level obtained by epidural analgesia (EA). We inserted a catheter into the epidural space through the L2/3 interspace, and hyperbaric tetracaine was injected through the L3/4 interspace with 26G spinal needle in thirty patients for CSE. We checked the the level of analgesia 90 min after spinal anesthesia. After this, 23 out of 30 patients showed the extension of analgesia 15 min after injection of mepivacaine into the epidural catheter. In these patients, the level of analgesia and the dose of mepivacaine showed the regression line Y = 10.2-0.4X (Y: the level of analgesia, X: the dose of 2% mepivacaine, P < 0.05). We also showed the regression line Y = 16.1-0.7X (P < 0.05) for EA 15 min after epidural injection of mepivacaine in other 23 patients. To achieve the same level of analgesia of Th8 or Th6 with CSE and EA, the doses for epidural injection were calculated as 5.5 ml, 10.5 ml with CSE and 11.5 ml, 14.4 ml with EA, respectively. These results show that the epidural dose of local anesthetic for CSE is 1/2 to 2/3 of that necessary for EA.

Adult↗

Stimulation of 5-HT1 receptors in the spinal cord changes substance P-induced behaviour.

This study examined whether intrathecal (i.th.) injection of different 5-hydroxytryptamine (5-HT) receptor agonists modulated the behavioural response to substance P. Given intrathecally, substance P produces a behavioural syndrome consisting of biting of the lower parts of the abdomen and reciprocal hindlimb scratching, which may be indicative of nociceptive stimulation. The number of substance P-induced bites was reduced when counted 5 min after intrathecal injection of 5-HT, p-chloroamphetamine (PCA) which causes release of 5-HT from neuronal terminals, the non-selective 5-HT receptor agonist quipazine, the selective 5-HT1 receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT], 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and 1(m-chlorophenyl)piperazine (mCPP), but was unchanged by treatment with the 5-HT2/5-HT1C receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The number of scratches was significantly increased 5 min after injection of 5-HT and RU 24969. The results showed that intrathecal injection of 5-HT agonists, with a high affinity for the 5-HT1 receptor subtypes, reduced the total number of responses induced by intrathecal injection of substance P, whereas a 5-HT2/5-HT1C receptor agonist did not affect the behavioural response to the intrathecal injection of substance P.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Pharmacological studies on lappaconitine: antinociception and inhibition of the spinal action of substance P and somatostatin.

The pain response of mice to an injection of 0.5% formalin into the dorsal surface of a hindpaw is biphasic, with a first phase lasting for 5 min and a second phase lasting from 10 to 30 min post-injection. Intrathecal (i.t.) injection of [D-Pro2, D-Trp7,9]-substance P inhibited the first phase, and i.t. cysteamine inhibited the second phase. Lappaconitine (LA) and morphine (MOR) inhibited both phases equally in a dose-dependent manner. Diclofenac inhibited both phases, but the second phase was inhibited by lower doses. An i.t. injection of substance P (SP) or somatostatin (SOM) produced a characteristic behavioral response (scratching, biting, and licking). This behavioral response to SP and SOM was inhibited by s.c., intracerebroventricular (i.c.v.), or i.t. injection of MOR. In contrast, LA inhibited the SP- and SOM-induced response when injected s.c. or i.c.v., but had no effect when injected intrathecally. These results indicate that LA may act supraspinally to inhibit the transmission of nociceptive information by SP and/or SOM.

Aconitine↗

Histopathology of the spinal cord after intrathecal cocaine, bupivacaine, lignocaine and adrenaline in the rat.

Repeated intrathecal injections were given through catheters which had been chronically implanted in the subarachnoid space of rats. Injections were made of cocaine 0.25%, 0.125% and 0.0625%; bupivacaine 0.5%; lignocaine 2% and 0.5%; adrenaline 0.01% (1 in 10 000) and 0.002% (1 in 200 000); and sodium chloride 0.9%. Five injections of 35 microliter of each concentration of each drug were given hourly each day for two days to three rats. No clinical nerve damage was detectable in any rat. The only pathological change found in any rat was the development of cytoplasmic vacuolation in the neurones of the anterior and posterior horns. The changes were most prominent after injection of 0.9% sodium chloride and bupivacaine, whilst lignocaine (0.5 and 2%) showed the least number of vacuoles, which were also the smallest in size. Adrenaline and cocaine were intermediate in effect. There was no evidence of cell death. These changes were not seen in control animals in which catheters had been implanted but no injections had been given. The changes were mild and it is concluded that the agents tested caused no significant damage.

Animals↗

Intraspinal and intracranial hemorrhage after lumbar puncture.

Two cases of spinal epidural hematoma and two cases of intracranial subdural hematoma after lumbar puncture (LP) are reported in children receiving chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma. The bleeding was asymptomatic but interfered with treatment in one case, and caused either severe backache or headache but no neurological deficit in the other three patients. The platelet counts were 8 and 46 x 10(9)/L in two patients and were normal in the other patients at the time of LP. All recovered without surgical treatment. There is an inherent, albeit uncommon, risk of bleeding into the central nervous system associated with LP in children with cancer and should be distinguished from postdural puncture headache (PDPH). Thrombocytopenia is not always an accompanying factor.

Adolescent↗

Respiratory depression associated with meperidine spinal anaesthesia.

Intrathecal meperidine administration can provide surgical anaesthesia and postoperative analgesia for about two to six hours. We have observed two cases of respiratory depression associated with meperidine spinal anaesthesia. An 81-yr-old woman received 50 mg intrathecal meperidine for inguinal hernia repair. Supplemental oxygen was administered at 3 L.min-1 by nasal prongs. About 40 min later, the patient's oxygen saturation decreased from 97% to 87% and she was asked to take big breaths. She responded immediately and oxygen saturation returned to 97%. Two more similar episodes followed in the next five minutes. Naloxone 0.1 mg iv was administered and the oxygen saturation remained at 96-97% until completion of surgery about 15 min later. She had an uneventful recovery. A 24-yr-old healthy woman presented for tubal ligation eight hours after vaginal delivery of an infant. The surgical procedure was performed under spinal anaesthesia produced by 50 mg meperidine. During surgery, midazolam 2 mg iv was given for anxiolysis. About five minutes after admission to the postanaesthesia care unit, the patient's respiratory rate decreased to ten breaths per minute and oxygen saturation decreased to 89%. Supplemental oxygen at 3 L.min-1 was administered by nasal prongs. The patient was encouraged to take big breaths and the arterial oxygen saturation rapidly increased to 98-99%. Forty minutes later, nasal oxygen was discontinued. The patient maintained her oxygen saturation while breathing room air. She was then discharged to the ward and had an uneventful recovery course. We recommend that a patient's respiratory variables and oxygenation be closely monitored for at least one hour after intrathecal meperidine administration.

Adult↗

Doxorubicin: a fluorescent neurotoxin retrogradely transported in the central nervous system.

Doxorubicin, a fluorescent cytotoxic antibiotic, was found to be both a retrograde neuron pathway tracer and neurotoxin to cells retrogradely labeled with it. Doxorubicin was injected into rat caudate-putamen and within 4 h the nuclei in the ipsilateral substantia nigra zona compacta (SNc) and ventral tegmental area (VTA) were stained with red fluorescent doxorubicin. After 2 weeks, portions, but not all of the ipsilateral SNc and VTA were depleted of neurons. Retrograde neurotoxicity was obvious following injections of 20%, 10%, 6%, 5% or 4% doxorubicin but not after 1% or 2%. Five months following doxorubicin treatment, the ipsilateral SNc and VTA were shrunken, distorted and nearly absent; the injected caudate was shrunken and replaced by ventricle. The ipsilateral thalamic parafasicular center median nucleus, a complex nucleus also known to project to the caudate, was depleted of large neurons 2 weeks following caudate injection. Doxorubicin can be transported over relatively long distances; lumbar spinal cord injections labeled cortical pyramidal neurons 3 days later. Doxorubicin's unique pathway-specific neurotoxicity may be useful in future neuroscientific studies.

Animals↗