Clinical Study Of Pregabalin In The Treatment Of Herpetic Neuralgia And Prevention For Post-herpetic Neuralgia

BackgroundHerpes zoster(HZ) results from the reactivation of endogenous varicella-zoster virus (VZV), which persisted in latent form within sensory ganglia following varicella. Pain following HZ usually is correspond with unilateral innervation area. Pain may occur before the rash onset or after, or together. For patients suffering from herpes zoster, VZV reactivation followed by replication induces neural and inflammatory changes in sensory ganglion and peripheral neurons. Although the shingles affect the peripheral sensory neurons, patients with neuralgia may show damage in the central nervous system (CNS) pain processing centers as well. Allodynia in a subset of patients may be caused by ectopic discharges from damaged C nociceptors maintaining a state of central sensitization. Acute herpetic neuralgia (AHN) is defined as pain that occurs within 30 days of rash onset. Subacute herpetic neuralgia (SHN) is defined as pain that persists beyond 30 days that persists for 90 days from the rash onset. Post herpetic neuralgia (PHN) is defined as pain presenting≥90 days that lasts after the acute herpes zoster rash has healed.The incidence of PHN was increasing gradually, especially with the population aging of our country, this trend became more obvious:the incidence of PHN in the Herpes Zoster patients,65% were over the age of 60, and 75% were over the age of 70. The occurrence of PHN reduced the patients’ quality of life severely, especially in elder patients. The severe pain might make patients with PHN the heavy psychological burden, depression, or even lose confidence to the life. While the present situation of PHN treatmentment was that some patients’pain still couldn’t be controlled completely.It is reported that pregabalin could inhibit the α2-δ subunit protein of voltage- gated calcium channel in the central nervous system, then reduce calcium ion flowing inward and reduce the release of excitatory neurotransmitters such as glutamate, norepinephrine, substance P etc. So that oral pregabalin could manage spontaneous pain, hyperalgesia and pain hypersensitivity that resulting from nerve injury effectively. The mechanism of pregabalin provides the theoretical basis for treating HZ neuralgia and preventing PHN by early application.Pregabalin has been recommended as the first-line dug for PHN therapy currently due to its efficacy and safety. However, there was no valuable report at present on the clinical efficacy of pregabalin for acute and subacute herpetic neuralgia, expect for a smaller study which included 29 outpatients who had acute zoster pain for a period of 7-14 days. And it is not clear whether early application of pregabalin can reduce the incidence of PHN. Therefore, this study was rational designed to evaluate the efficacy and safety of pregabalin in the treatment of herpetic neuralgia, and follow-up to the 12th week, evaluation whether impacting the accidence of PHN. It is the first time in the international that treating AHN and SHN with pregabalin as a large sample size clinical trial. The results of this study will be great significance for guiding the clinical medication.ObjectiveTo evaluate the efficacy and safety of pregabalin in the treatment of herpetic neuralgia. And follow-up to the 12th week, evaluation whether impacting the accidence of PHN. Evaluate the clinic application value of pregabalin in the treatment of herpetic neuralgia totally.MethodsIt is a multicenter, parallel-group, single-blind, randomized clinical trial. The study subjects were patients with AHN or SHN. A total of 300 subjects were randomly divided into two groups, respectively treated with oxycodone (A group) or combination of oxycodone and pregabalin (B group). Patients with AHN belonged to A1 group and B1 group. Patients with SHN belonged to A2 group and B2 group. Pain intensity was rated on an 11-point numerical rating scale (NRS). Quality of life was rated on Brief Pain Inventory (BPI). Other outcomes included mean daily oxycodone doses and adverse effects. SPSS V17.0 statistical software package was used for statistical analysis. P<0.05 was considered to be significant.Results Finally total of 239 patients completed this research.1. General informationThere were no differences in common data among all the patients (P>0.05).2. Pain IntensityAfter the treatment, all the 4 groups resulted in significant NRS decrement compared with baseline. On day 7, the mean NRS scores for all the 4 groups decrease 2 or more than 2 point. At the end of therapy, the mean NRS scores for patients in the B1 groups had decreased by 74% (vs.58% in A1, P<0.05), and 69% in B2 group (vs.53% in A2, P<0.05).3. Mean Daily Doses of OxycodoneIn the 4 groups, the mean daily doses of CR oxycodone were the same 20 mg at the beginning. At the end of therapy, the mean daily doses were 48.2±10.9 mg in A1 group, 51.8±12.1 mg in A2 group,38.2±12.7 mg in B1 group (35.5% less than that in A1 group, P>0.05) and 42.5±12.4 mg in B2 group (29.2% less than that in A2 group, P>0.05), respectively.4. Quality of LifeFor patients in all the groups, treatments resulted in improvement of the quality-of-life parameters. At the end of the treatment, the overall decrease of BPI scores compared with the baseline was 72.7% in B1 group (vs.63.7% in A1 group, P<0.05) and 74.5% in B2 group (vs.59.6% in A2 group, P<0.05).5. Safety AnalysisOverall, safety of the treatment for the 4 groups was similar. The common adverse events in the A1 and A2 group were constipation and nausea/vomiting. However, the common adverse events in the B1 and B2 group were somnolence, dry mouth and peripheral edema. There were no significant differences(P>0.05).6. The accidence of PHNThe accidence of PHN in B group treated with pregabalin decreased obviously comparing with A group (B1 33.3.% vs. A1 47.6%, P<0.05; B2 43.8% vs. A2 52.0%, P<0.05). And the accident in B1 decreased more obviously than B2 group (B1 33.3% vs. B2 43.8%, P<0.05).ConclusionBoth combination therapy with oxycodone plus pregablin and oxycodone monotherapy were effective and safe for herpetic neuralgia. In addition, combination therapy could shorten the time of pain, reach to pain relief rapidly, reduce the pain intensity, and showed greater improvement than oxycodone alone. And the accidence of PHN could be decreased by treating with pregabalin for AHN or SHN.