Analgesic effect of subarachnoid neostigmine in two patients with cancer pain

Abstract

Two patients suffering with severe pain due to metastatic abdominal neoplasm were selected to examine whether subarachnoid neostigmine provided effective pain relief. Neostigmine was injected through a catheter introduced into the subarachnoid space at L4-L5. Patients were monitored for changes in arterial blood pressure, cardiac and respiratory rates, body temperature, level of consciousness and neurologic change. Pain was classified by the patients on a verbal four-grade scale, and analgesia was classified on a verbal three-grade scale. Complete pain relief was obtained 2 h after neostigmine (0.2 mg) in one patient and 4 h after neostigmine (0.1 mg) in the second patient. Pain of mild intensity returned 20 and 22 h after drug administration, respectively. Gastrointestinal discomfort was observed in both cases, but nausea and vomiting occurred only in the patient treated with the highest dose of neostigmine. No significant change in the monitored parameters was observed, except for a 6-h period of decreased blood pressure in the patient treated with the lower dose of neostigmine which required no specific treatment. The results obtained in these anecdotal cases indicate that subarachnoid neostigmine may provide analgesia in patients with pain arising from neoplasia, but further studies using controlled trials are needed before the drug is brought into clinical use.

Caudal neostigmine with bupivacaine produces a dose-independent analgesic effect in children

“…11,[15][16][17][18] Spinal delivery of the cholinesterase inhibitor neostigmine inhibits the breakdown of the endogenous spinal neurotransmitter acetylcholine which has been shown to produce analgesia. [19][20][21] Neuraxial administration of neostigmine increases the concentration of acetylcholine in cerebrospinal fluid and produces antinociception in animals which is blocked by the intrathecal administration of a muscarinic antagonist.…”

“…[19][20][21] Neuraxial administration of neostigmine increases the concentration of acetylcholine in cerebrospinal fluid and produces antinociception in animals which is blocked by the intrathecal administration of a muscarinic antagonist. [15][16][17][18][19][20][21][22] The analgesic effect is thought to be mediated via spinal muscarinic M 1 receptors and supraspinal muscarinic M 1 and M 2 and nicotinic cholinergic receptors. 15,22 Autoradiographic studies 10.0 ± 2.1 9.8 ± 1.6 9.5 ± 1.6 9.7 ± 2.3…”

Antinociceptive effect of intrathecal neostigmine evaluated in rats by two different pain models

“…The intraspinal administration of neostigmine produces long-lasting analgesia in laboratory animals (1) and volunteers (14,15), and permits the management of both postoperative (16) and cancer pain (17). The antinociceptive effect of manipulating the central cholinergic system, however, seems to depend on the animal species and/or algesimetric assay utilized (see Ref.…”

Effect of lumbar epidural administration of neostigmine on lower urinary tract function

“…1 Over 13 years of its clinical existence as intrathecal analgesic, Neostigmine has stood the test of time and has proven dose-dependent efficacy and good tolerability for both acute as well as chronic pain in dosage of 100-750 mg; most commonly used dosage for pain relief is 1-4 mg/kg body weight. 3,4,11 In our series, we used its 2 mg/kg body weight dose by epidural route and we found that Neostigmine provided good analgesic effect during rigid cystoscopy; median VAS pain score of 1 (range 0-3) compared to median 4 (range 3-7) in age-matched controls (P ¼ 0.0001). It has also been studied as adjunctive analgesic (dose of Neostigmine mentioned in parentheses) to various neuroaxially administered drugs, for example, lidocaine (1-4 mg/kg 19 ), intrathecal Bupivacaine (25-75 mg) 20 , epidural Ropivacaine (2-4 mg/kg), 21 and morphine (60 mg), 5 etc., and found to be useful in reducing drug dose, increasing analgesia duration, and decreasing opioid requirement.…”

“…1 After preclinical toxicity screening, the polar cholinesterase inhibitor, Neostigmine was introduced into clinical trials in 1995 for intrathecal injection 2 and has been found effective in chronic as well as postoperative pain. [3][4][5][6][7] Nausea and sedation are significant side effects of intrathecal administration of this drug which are uncommonly observed with epidural administration. 2,5 -8 Cholinergic side effects, for example, sweating, salivation, and abdominal cramping are exceedingly rare.…”