Relief for Postherpetic Neuralgia

Abstract & Commentary

Source: Kotani N, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;343:1514-1519.

Methylprednisolone was administered intrathecally, once-a-week for up to four weeks, in this randomized, blinded, controlled, clinical trial of 277 patients, to determine its efficacy for postherpetic neuralgia (PHN) involving spinal dermatomes. All patients had intractable PHN, defined as at least one year of burning, lancinating pain with allodynia in the originally affected dermatome. Exclusionary criteria included trigeminal area pain, prior neurolytic nerve blocks, polyneuropathy, or an immunocompromised state. On study entry, all patients received conventional systemic treatment (tricyclic antidepressants, anticonvulsants, topical creams, physiotherapy) for four to six weeks, if not previously tried, followed by oral diclofenac for four weeks. Those with persistent pain were then randomized to intrathecal methylprednisolone (60 mg) plus 3% lidocaine (3 mL), or intrathecal lidocaine alone, or no treatment (control, no lumbar puncture). Only oral diclofenac, up to 200 mg/d, was permitted during the treatment and follow-up period. Patients were followed for two years. Primary end points included 10-cm visual-analogue scale assessments of pain, allodynia, and global pain relief, measurement of the maximally affected surface area as traced by an ink marker, and measurement of interleukin-8 cerebrospinal fluid concentration, elevation of which is associated with painful inflammatory conditions. Statistical analysis included one-way factorial analysis of variance, Scheffe’s test, and chi-square analysis.

Astonishingly, 91% (81/89) of the methylprednisolone plus lidocaine group experienced good (50-75%) to excellent (> 75%) global pain relief. This compared to 15% (14/91) and 4% (4/90) at treatment-end in the lidocaine only and control groups, respectively, and 7% (6/91) and 3% (3/90) at four weeks post-treatment and beyond. Allodynia, burning pain, lancinating pain, and diclofenac usage were reduced by 70%, and interleukin-8 cerebrospinal fluid concentration by 50% in the methylprednisolone plus lidocaine group. This was compared to significantly less or no improvement in the other groups. No adverse effects or recurrent pain were recorded over two years in the methylprednisolone plus lidocaine group. Intrathecal methylprednisolone plus lidocaine appears safe and effective for intractable noncranial postherpetic neuralgia, but longer follow-up of larger numbers of patients will be necessary to ensure that worrisome adverse effects, including adhesive arachnoiditis, have not occurred.

Commentary

A milliliter of prevention is worth a kilogram of cure. Can PHN be prevented? In a randomized, prospective trial, 600 acute herpes zoster patients older than age 55 received either intravenous acyclovir (10 mg/kg thrice daily for 9 days) plus prednisolone (60 mg daily with tapering over 3 weeks), or epidural bupivicaine (0.25%, 6-12 mL q 6-8 or 12 h) plus methylprednisolone (40 mg every 3-4 days) for 1-3 weeks, as needed (Acta Anaesthesiol Scand 2000;44:910-918). Evaluations were performed four times over the following year and included measurements of pain using a 10-cm visual analog scale, paresthesiae using a 4-point verbal rating scale, or complete recovery. Statistical analyses were performed using two-tailed Z tests and X2 tests, the Mann-Whitney U-test, and Fisher’s exact test.

Of 485 patients who completed the study, only 1.6% (4/255) of the epidural treated group complained of pain, compared to 22.2% of the intravenous group. Paresthesiae were noted in 4.3% (n = 11) and 12.2% (n = 28), respectively. Adverse effects in the intravenous group were predominantly gastrointestinal in nature. Episodic sweating or fainting (n = 2), neck pain or leg paresis (n = 1 each), and catheter dislodgment (n = 9) were reported in the epidural group. All adverse effects were reversible. Epidural bupivicaine and methylprednisolone appear significantly more effective than intravenous acyclovir plus prednisolone in preventing PHN and, pending confirmatory studies demonstrating its safety and efficacy, should be considered early on in patients at high risk of developing this disabling condition.

Once PHN develops, what therapeutic options exist? The Table below summarizes the scientific literature. —Michael Rubin

 

Table: Choices for PHN Treatment

Drug 

Effectiveness

Topical capsaicin

 Conflicting evidence as to benefit

Nonsteroidal creams

Of questionable value

Aspirin suspended in
chloroform, ether, or acetone

Of questionable value

EMLA cream

Of questionable value

Lidocaine patch (LidodermTM)
(Pain 1999;80:533-538.)

Approved by FDA for PHN

Tricyclics 

Most widely used AD for
chronic pain

SSRIs (Pain 1990;42:135-144;
Clin Pharmacol Ther 1992;52:547-552.)

May be efficacious

SNRIs (venlafaxine [Effexor]) (West J Med 1996;165:147-148.)

May be efficacious

Gabapentin (JAMA 1998;280:1837-1842.)

Of proven advantage

Oxycodone
(Neurology 1998;50:1837-1841.)

Of proven advantage

Tramadol
(Clin Drug Invest 1995;10:208-214.)

May be beneficial

Ketamine (NMDA receptor antagonist)
(Clin J Pain 1994; 10:240-242; Clin J Pain 1995;11:336-338) 

May be beneficial, but hepatotoxic

Dextromethorphan
(Neurology 1997;48:1212-1218.)

Of no benefit

Food and Drug Administration (FDA); post herpetic neuralgia (PHN); antidepressant (AD); selective serotonin reuptake inhibitors (SSRIs); serotonin-norepinephrine reuptake inhibitor (SNRIs); N-methyl-D-aspartate (NMDA)