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Acute Pain | Chronic Pain | General

Systemic local anaesthetic-type drugs in chronic pain

Clinical bottom line:

Sodium channel blockers can be used to reduce pain due to nerve damage. Intravenous lignocaine and oral mexiletine both reduce neuropathic pain. Intravenous lignocaine is effective in fibromyalgia (based on small patient numbers), but not in cancer related pain. Intranasal lignocaine is not effective in myofascial pain (based on small patient numbers).


Lignocaine and related local anaesthetic-type drugs which block sodium channels have been used to relieve clinical pain, as a last resort in cancer-related pain and in other conditions when more traditional treatments fail. It has been demonstrated that the neuroma and the dorsal root ganglion display spontaneous activity and increased sensitivity after peripheral nerve injury. Systemic sodium channel blockers silence the spontaneous activity, and may block glutamate-evoked activity in the dorsal horn of the spinal cord.

Systematic review

Kalso E, Tramèr M R, Moore RA, McQuay HJ. Systemic local anaesthetic type drugs in chronic pain: a qualitative systematic review. Eur J Pain. 1998; 2: 3-14.

Inclusion criteria were randomised controlled trials of local anaesthetic-type drugs for pain relief; pain outcomes.

Findings

Neuropathic pain

Nine trials were included, with 199 patients and the following pain conditions: peripheral nerve injury, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia and dysaesthetic pain following spinal cord injury.

Peripheral nerve injury: Two of two trials showed significantly better pain relief with intravenous lignocaine (intravenous 2 and 5 mg/kg over 45 mins) compared with placebo, and a dose response. One of these trials also showed significant reduction of allodynia. One of one trials showed significantly better pain relief with mexiletine (oral up to 750 mg/day) compared with placebo in patients with peripheral nerve damage of mixed origin.

Diabetic neuropathy: One of one trials showed a significant effect of lignocaine (intravenous 5 mg/kg over 30 mins) up to eight days compared with placebo, and significant relief of dysaesthesia. One of two trials showed significantly better pain relief with mexiletine (oral 750 mg/day) than placebo. The second trial only showed benefit with post hoc analysis of subgroups.

Postherpetic neuralgia: One of one trials showed lignocaine (intravenous 2.4 to 6.0 mg/kg over one hour) significantly better than placebo, but inferior to intravenous morphine.

Dysaesthetic spinal cord injury: One of one trials showed no benefit of mexiletine (oral 450 mg/day) compared with placebo in reducing dysaesthetic pain following spinal cord injury.

Trigeminal neuralgia: One of one trials showed that tocainide (oral 1500 mg/day) was comparable to carbamazepine (oral maximum tolerated dose).

Figure: Analgesic efficacy with active (intranous lignocaine or oral mexiletine) compared with placebo.

Decrease in pain intensity from baseline (before start of treatment) to end of treatment. Each symbol is one trial.

Fibromyalgia

One trial was included. Based on 11 patients, pain relief was significantly better with lignocaine (5 mg/kg over 30 mins) at 15 minutes, and at least 50% pain relief persisted for 4-7 days in three of four responders.

Myofascial facial pain

One trial of 28 patients showed lignocaine (intranasal 30 mg) was not significantly better than placebo.

Cancer-related pain

Three small trials compared lignocaine (intravenous 5 mg/kg) with placebo. In three of three trials lignocaine was no different to placebo (conditions: bony metastases, chemotherapy polyneuropathy, radiotherapy plexopathy, tumour invasion of nerve plexus).

Adverse effects

No arrhythmias were noted in any trial with lignocaine infusion (all but one measured this). Twenty-one of 134 infusions were associated with adverse effects (mainly light-headedness, somnolence, nausea and perioral numbness). Five of these resulted in study withdrawal. One adverse effect was reported in 100 saline infusions. Dose-related adverse effects were reported in 16 of 85 mexiletine patients. These were considered mild, and there were no study withdrawals. Tocainide was associated with three adverse effects in 12 patients (nausea, apical paraesthesias and skin rash), but is known to cause serious haematological adverse effects including death.

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