Introduction

Neuropathic pain originates from a dysfunction or a damage of the central or peripheral nervous system₁,₂. According to the site of the lesion in the nervous system the neuropathic pain can be classified as central or periferic₂. Clinically neuropathic pain is characterized as chronic course, is described by the patients as lancinating, burning, accompanied by smart, electric shock, pins and needles and paresthesia₂,₄. Pain can be spontaneous or provoked, with evocation of allodynia and/or hyperalgesia. Neuropathic pain can be serious and invalidating; it may and compromise the life quality with interference on the sleep and humor₃. Peripheral neuropathic pain includes diabetic neuropathy, trigeminal neuralgia, post-herpetic neuralgia, reflex sympathetic dystrophy, post laminectomy syndrome, post-entrapment syndrome, ghost limb syndrome, radiculitis and entrapment neuropathies. Pregabalin (the S-3-aminometil-5acido-metilesanoic) has anticonvulsive and analgesic activity; studies in vitro and experimental models show that pregabalin is a selective binder with high affinity₁₁to voltage dependent calcium channels X receptors α 2 - δ in the SNC₅,₆,₈; such connection reduces the depolarization induced from the income of calcium and diminishes the release of neurotransmitters (noradrenalin, glutamate, substance-P) in the hyper excited neurons₅,₆,₁₂,₁₃. Pregabalin prevents the reactions to pain in neuropathic pain animal models, even in allodynia and hyperalgesia₇,₈. Pregabalin is indicated in the treatment of peripheral neurophatic pain.

Aim Of The Study

The aim of the study is the evaluation of the effectiveness and safety of Pregabalin for treatment of chronic peripheral neuropathic not oncological pain in adults.

Materials And Methods

Criteria of inclusion: aged between 18 and 80 years, presence of not oncologic peripheral neuropathic pain. Criteria of exclusion: hypersensitivity versus Pregabalin, pregnancy, renal insufficiency, alcohol poisoning, use of psychotropic drugs, use of drugs commonly used in the neuropathic pain (antiepileptics, benzodiazepines, gabapentin, tricyclics, etc.). All patients were informed and signed per consensus as italian legislative dispositions prescribed. The basal evaluation card compilation has taken in consideration: patient's age, pathology and type of pain, symptoms and signs of peripheral neurosuffering at the beginning and at the end of therapy cycle with the Pregabalin, the analgesic therapy at the beginning of the study, the VAS (Visual Analogue Scales) ₉ and Karnofsky Performance Status ₉ at the beginning of the therapy, at the term of 12^th week of therapy and 2 months from the suspension of the drug. The selected patients were submitted to a cycle of therapy with Pregabalin at a flexible dosage of 150-600 mg/die in two every day administrations; such posologic regimen has turned out to be more favourable at fixed dose in terms of tolerability and individual answer ₄. We started with 150 mg/die and we increased the dosage up to 300-600 mg/die weekly based on the therapeutic answer and collateral effects; the therapeutic dosage was continued for 12 weeks; it was moreover made a control at a distance of 2 months from the drug administration term. The design of the study is represented in fig. 1.

Figure 1

Figure 1

Results

The studied population was of 33 patients, 60.6% (n=20) of feminine sex, 39.4% (n=13) male; the average age is of 58,87 years with standard deviation of 13,83, median of 64 and mode of 69; range of age from 27 years to 76 (Tab1).

Figure 2

Table 1

64% of the patients (n=21) recruited have finished the study protocol, while 36% (n=12) (C.I. 22% - 53%) have interrupted the assumption of the Pregabalin. The subclass of pathologies with peripheral neuropathic pathology treated have been: lower back pain (n=10), diabetic neuropathy (n=2), vertebral cervical pain (n=2), vertebral crack (n=2), ghost limb syndrome (n=1), coccyx pain (n=1), post-herpetic neuralgia (n=1), trigeminal neuralgia (n=1) and anal pain (n=1). Because the distribution of the values of VAS and Karnofski performance status (KPF) wasn't normal, we have used non parametric tests for the statistical analysis: Wilcoxon rank test and the sign test (Tab 2, 3, 4, 5).

Figure 3

Table 2

Figure 4

Table 3

Figure 5

Table 4

Figure 6

Table 5

They show a significant decrease of the pain and improvement of the life quality after therapy and in the follow up. Collateral effects were registered in 36% (22%-53%) of the cases: the most common were confusion (n=3), sleepiness (n=3), epigastralgia (n=2), vertigos, arterial hypertension, headache and generalized oedema (n=1 for each type).

Conclusions

Pregabalin statistically turned out to be effective in peripheral neuropathic not oncological pain treatment, in terms of diminishing pain and in terms of life quality. Two patients haven't had any clinical benefit, while 4 patients had benefit from the treatment but, at the 2 months from the suspension of the drug control, clinical condition was the same as at the beginning of therapy. 42% (24%-62%) of the studied population had clinical benefit at the dosage of 150 mg/die, 24% (11%-45%) at 300 mg/die and 34% (18%-55%) at the maximum dosage of 600 mg/die. Therefore in 68% (47%-84%) of the patients it wasn't necessary to reach the maximum dosage, with consequent better compliance and tolerability. A high percentage of collateral effects was registered (36% (22%-53%) of the population), which induced drug suspension. The most frequent collateral effects were confusion and drowsiness.

Correspondence to

G. B. Venier, E. mail: gbvenier@asl14chioggia.veneto.it tel. 0415534338, Fax 0415534394.