Analgesic Effect In Neuropathic Pain Research Articles

Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial

The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or 20 mg of oral methadone were evaluated in 18 patients with a diverse range of chronic neuropathic pain syndromes, who had all responded poorly to traditional analgesic regimens. Analgesia was seen after each dose of methadone. As compared with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale ratings of maximum pain intensity, average pain intensity and pain relief, recorded at the same time daily. The analgesic effects extended over 48 hours, as shown by statistically significant (P = 0.013-0.020) improvements in all three outcomes on the rest days instituted between each daily dose. Analgesic effects (lowered maximum pain intensity and increased pain relief, on the day of dosing only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg bd) was used, but these failed to reach statistical significance (P = 0.064 and 0.065, respectively). Interpatient analysis showed that the analgesic effects were not restricted to any particular type of neuropathic pain. Patient compliance was high throughout the trial. One patient withdrew during the 10 mg and six during the 20 mg methadone treatment periods. This is the first double-blind randomized controlled trial to demonstrate that methadone has an analgesic effect in neuropathic pain.

Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain

We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i) vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii) vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii) the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED 50 of morphine 10-fold; (iv) animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v) vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.

Pharmacological management of neuropathic pain.

In health, the nervous system exists in a balance between inhibitory and excitatory influences. This balance may be upset if neural tissue is damaged or irritated and may give rise to neuropathic pain. Such neuropathic pain does not respond consistently to opioid analgesics or NSAIDs and it may therefore be necessary to utilise other therapeutic agents with known activity on either the excitatory or inhibitory components of the pain pathway. These other agents are traditionally considered with reference to their original uses; we still refer to tricyclic antidepressants (TCAs) and anticonvulsant drugs when a consideration of their modes of action may allow more rational use. For example, carbamazepine is related to the TCAs by virtue of its chemical structure and proposed mode of action and yet is still classified as an anticonvulsant drug. With respect to the opioids, increasing evidence points to an analgesic effect in neuropathic pain, although concerns regarding tolerance and dependence still prevent more widespread use. The anticonvulsants comprise a group of compounds possessing anticonvulsant and analgesic properties, but each possesses differing modes of action and so several members of the class should be tried before a conclusion is reached that they, as a whole, are ineffective. TCAs may also have a role in the treatment of neuropathic pain. As with all drugs, if their use is not associated with pain relief in a defined period of time, their use should be terminated. Topical TCAs may also have a role where the area of neuropathic pain is small. Other options, such as SSRIs, membrane stabilisers, capsaicin, baclofen and clonidine may have potential in treating neuropathic pain. The available evidence regarding the efficacy of currently available agents for the treatment of neuropathic pain is sparse. With the knowledge of achieving analgesia, according to the modes of actions of various agents it is hoped that the treatment of this difficult condition may be more logical and successful.

Response

Drs Gilder and Brown correctly point out that the dose escalation described in my case report is contrary to the manufacturer's guidelines. However, the reason for using the dose escalation regime described is that this has been our normal clinical practice over the last 5 years of use of lamotrigine in many hundreds of patients. Furthermore, we have published a blinded, randomized controlled trial using the dose escalation suggested by Glaxo-Wellcome and found no analgesic effect when lamotrigine was used in a dose increased to 200 mg daily. 1 McCleane GJ 200 mg Lamotrigine has no analgesic effect in neuropathic pain: A randomized, double-blind placebo-controlled trial. Pain. 1999; 83: 105-107 Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar This is very much at odds with our clinical experience with the drug. A possible reason for this conflict is the differing dose escalation regime. When a drug produces the desired effect in clinical practice when used in a particular fashion, it is hard to change its use to a method that is proven not to be effective.

Topical doxepin hydrochloride reduces neuropathic pain: a randomized, double-blind, placebo controlled study

Tricyclic antidepressants have a proven efficacy in neuropathic pain but their use is frequently complicated by side-effects. In a randomized, double-blind, placebo controlled study we compared the effect of twice daily application of doxepin hydrochloride 5% and placebo in forty patients with neuropathic pain. Results were obtained from 75% of those enrolled. There was a significant reduction in pain scores (linear visual analogue scores, 0-10) in those treated with topical doxepin hydrochloride when compared to placebo (mean fall in doxepin group 1.18, P < 0.01). minor side-effects were seen in 3 patients. there was no significant difference drowsiness levels in the two groups.We conclude that topical doxepin hydrochloride has an analgesic effect in neuropathic pain and its use is not commonly complicated by side-effects.

200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial

Anticonvulsant drugs are commonly used in neuropathic pain. There is anecdotal evidence of an analgesic effect of the anticonvulsant lamotrigine in neuropathic pain, but this is verified by few randomised controlled trials. This randomised, double-blind, placebo controlled trial of examined the effect of lamotrigine in a dose increasing to 200 mg in 100 patients with neuropathic pain. Eight patients failed to attend for review, 18 withdrew early and 74 provided results. There was no statistical difference in age, sex or duration pre-treatment pain in the two groups. Total pain, the character of the pain, sensitivity, numbness, paraesthesia, sleep, mobility, mood, quality of life and analgesic consumption were measured. There was a correlation between burning and numbness ( P<0.01), shooting pain and total pain ( P<0.01) and between analgesic consumption and mobility ( P<0.05) throughout the study period. There were no correlation between any other measured variable. There was no significant change in any variable measured over the eight week period when lamotrigine was used. It is concluded that at the dose used and using the dose escalation regime described, lamotrigine had no effect on either pain, component pain symptoms or quality of life variables.

The consumption of fentanyl is increased in rats with nociceptive but not with neuropathic pain

The question whether opioids relieve neuropathic pain remains a controversial issue. Experimental as well as clinical studies report contradictory results. This study investigated the consumption of fentanyl, a short-acting opioid, in rats with neuropathic pain, induced by partial sciatic nerve injury. The experiment consisted of a drug choice procedure in which the animals could choose between a solution containing 0.008 mg/ml of fentanyl and a highly palatable sweet solution. It was reasoned that if opioids have an analgesic effect in neuropathic pain, this will reinforce the intake of fentanyl more so in rats with neuropathic pain than in pain-free controls. This protocol was previously already used by Colpaert et al. (1982) in a rat model of chronic pain of nociceptive origin, namely polyarthritis. No significant differences were found in the relative oral intake of the fentanyl solution in mononeuropathic and pain-free control rats. In contrast, rats with nociceptive pain, adjuvant monoarthritis, drank significantly more of the fentanyl solution than did control rats. These data give experimental support for the clinical findings that opioids have a poor analgesic effect in neuropathic pain.