Conclusion evidencebased treatment of central pain

Treatment algorithm in CP

It is difficult to suggest a treatment algorithm based on randomized controlled trials within each of the above-mentioned central pain conditions and impossible in more rare central pain conditions. Peripheral and central pain conditions share common clinical characteristics and it is likely that some of the underlying mechanisms may be similar. Most drugs suggested to be effective in neuropathic pain (TCA, SNRI, gabapentin/pregabalin, opioids and tramadol) are nonspecific and act at multiple sites in both the peripheral and central nervous systems. So far, there is no evidence to suggest that these drugs/drug classes are effective in only some neuropathic pain conditions and it is rational to expect some overlap in efficacy in various central pain conditions and probably also to translate efficacy from peripheral to central pain conditions.

Pregabalin and gabapentin, whose analgesic action is thought to occur via binding to the a 2 8 subunit of voltage-gated calcium channels, have been found effective in both central and peripheral pain syndromes and are normally well tolerated [13, 23, 41]. Therefore we recommend pregabalin/gabapentin as first-line treatment of CP. The efficacy of TCA is documented in peripheral neuropathic pain conditions, whereas the results of randomized trials in different CP conditions are somewhat more conflicting. Amitriptyline reduced CPSP [11] but was ineffective in SCI pain [24]. However, in the SCI trial the primary endpoint was overall pain, not neuropathic pain. The results in peripheral neuropathic pain are very consistent [41] and TCA are therefore recommended here as the second choice of treatment in CP. No RCT have evaluated the efficacy of SNRI in central pain, whereas this class of drugs has shown a moderate effect on pain in painful polyneuropathy [41]. The possible side effects of TCA may limit their use and in patients with cardiac disease, SNRI may be a safer choice.

Lamotrigine has been shown to reduce pain in CPSP in one trial [14] but in SCI pain, there was no effect of lamotrigine although there was some suggestion that it reduced pain in the subgroup of patients with incomplete SCI [26]. Lamotrigine has few side effects and slow dose escalation limits the risk of serious allergic reactions and so it may be considered an alternative analgesic in central pain.

Cannabinoids were shown to be effective in reducing MS-related central pain and were well tolerated in low-dose regimens [46, 49]. However, possible long-term effects including psychiatric symptoms have not been ruled out and cannabi-noids are therefore not recommended as first-line treatment in CP. The same is true of opioids and tramadol, in which long-term side effects and drug addiction are concerns. Small studies in CP have failed to document an effect of opioids in stroke patients [16] and MS patients [48]. However, opi-oids as well as tramadol are effective in reducing peripheral neuropathic pain and may also be considered in refractory CP.

There is a good rationale for combining drugs with different modes of action as this may lower the frequency and severity of side effects and have additive and maybe even synergistic effects but there is little clinical evidence for these assumptions.

Thus, based on efficacy in CP and peripheral neuropathic pain [55], as well as considering side effects and long-tem risks, a treatment algorithm for CP may look as suggested in Figure 21.1.

Central pain

First choice

Second choices

Third choices

Central pain

First choice

Second choices

Third choices

Figure 21.1 Proposed treatment algorithm for central pain conditions (trigeminal neuralgia in MS not included).

Future studies may reveal whether a mechanism-based treatment classification is more useful than the traditional disease-based classification.

Nonpharmacologic treatment of CP

New trials on single and repetitive transcranial magnetic stimulation suggest transient efficacy in central pain (Level B recommendation) and may be predictive of efficacy with implanted motor cortex stimulation [56 -58]. Motor cortex stimulation may reduce pain in about 50% of CPSP patients as shown by two class III studies (for review see reference 58). Very few studies have been conducted evaluating the efficacy of deep brain stimulation (DBS) on central pain and the results are conflicting. Therefore the recommendation of the European Federation of Neurological Societies (EFNS) is only to perform DBS in experienced centers with established outcome measures [58].

The difficulties in obtaining optimal pain relief in CP conditions by pharmacologic intervention emphasize the need for a multidisciplinary approach. Nonpharmacologic treatment regimens including physiotherapy, cognitive and behavioral therapy are often used. Norbrink et al. [59] performed a non-randomized study, in which a multidisciplinary pain program was evaluated in patients with SCI and neuropathic pain. The 10-week program included educational sessions on pain physiology/pharmacology, behavioral therapy, relaxation techniques and body awareness training and included 27 patients with SCI. A control group consisting of 11 patients with neuropathic pain was included. At 12-month follow-up no effect was seen on pain intensity, but the level of anxiety and depression decreased. Other methods such as hypnosis may also be useful.

Future research

There is a strong need for more randomized clinical studies in optimizing the treatment of CP. Large-scale multicenter studies on both pharmacologic and nonpharmacologic treatments are warranted. Studies evaluating the efficacy of combining different analgesics could give us more information about possible synergistic effects. In the evaluation of treatment efficacy, simple psychometric scales on pain intensity and quality of life measures are recommended [60]. The intensity of different pain qualities (including spontaneous and evoked pain) should be measured separately, enabling us to assess the possibility of a mechanism-based treatment. Functional neuroimaging may in the future give us a better understanding of central pain processing and pathophysiologic differences in spontaneous and provoked pain.

Authors' recommendations

Currently only a few clinical studies are available to guide us in the treatment of the individual patient with CP. However, we recommend that clinicians follow the evidence based treatment algorithm given in Figure 21.1. In our opinion, this is the best treatment option at the time of writing.

It is well known that the outcome of pharmaco-therapeutic treatment of neuropathic pain (including CP) is poor. Only 30 - 40% of patients will achieve a target of at least 50% pain reduction. Therefore, we recommend that a multidisciplinary team (including pain nurses, physiotherapists and psychologists) is established at the pain clinic to help patients to cope with the pain. Invasive procedures such as DBS need further documentation on therapy for CP and are not recommended at this time.

Acknowledgments

Dr Jensen has received research support, consulting fees or honoraria in the past year from Eli Lilly, Lundbeck Research Foundation, Neurosearch, and Pfizer. Dr Finnerup has received research support or honoraria in the past year from Pfizer, Neurosearch, UCB Nordic, Endo Pharmaceuticals, and Mundipharma.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook


Post a comment