AHN is defined by the International Herpes Management Forum (IHMF®
) as the pain from onset of prodrome to 30 days; pain between 30 days from prodrome onset to 4 months is subacute herpetic neuralgia; and pain persisting beyond 4 months from onset of the prodrome of herpes zoster is post herpetic neuralgia.[2
] The role of gabapentin in reducing the pain of post herpetic neuralgia is well established.[4
] In most of the earlier studies, gabapentin was started after 30 days to 3 months from the onset of zoster. These studies showed significant role of gabapentin in the chronic pain of PHN. In our study, gabapentin was started as early as possible after the diagnosis of zoster.
The pathophysiology of pain in acute herpetic neuralgia differs from that of PHN. In acute zoster, the skin is inflamed, already partially denervated and the dorsal-root ganglion shows inflammation, hemorrhagic necrosis, and neuronal loss.[7
] On the other hand, PHN is due to the continuing inflammation in peripheral nerves for weeks to months leading to demyelination, wallerian degeneration, and sclerosis.[8
] After the injury, peripheral neurons discharge spontaneously, have lower activation thresholds, display exaggerated responses to stimuli, and there is an altered central nervous system signal processing.
] Gabapentin has been reported to relieve pain in patients with intractable neuropathic pain and reflex sympathetic dystrophy allowing the reduction or termination of other analgesic medications and relieving symptoms associated with painful disease manifestations.[10
] It also reduces spontaneous pain and tactile allodynia in patients with peripheral or central pain.[5
] We utilized the property of gabapentin to act both centrally and peripherally by starting gabapentin within 72 hours of onset of zoster.
This study shows that gabapentin in all doses was significantly more efficacious than placebo (P
<0.001). Comparison between different doses showed significantly less efficacy of 300 mg/day as compared to 600 and 900 mg per day (P
<0.001) and dosage of 600 mg/day was equally efficacious to 900 mg/day (P
>0.05). This effect can be explained on the basis of nonlinear-bioavailability relationship of gabapentin, i.e., at higher doses smaller percentage of drug is bioavailable.[11
While reviewing the literature, we could find only two studies published in western text assessing the role of gabapentin in acute herpetic neuralgia. Berry and Peterson observed 66% reduction of pain as compared to placebo by using single dose 900 mg of gabapentin.[12
] Our study also showed around 26-38% of reduction of pain in different groups as measured by VAS at the end of 4th
week. It should be noted that in the former study, the effect was studied for six hours period only, while in our study, the effect was observed for four weeks period showing the long term efficacy of the drug. Another study by Dworkin et al
., on gabapentin and CR-oxycodone (controlled release) showed significant reduction in pain with oxycodone in the first two weeks, but for gabapentin, the pain relief was observed only in the first week but not later.[13
] In our study, the pain reduction started by the end of first week of therapy was highest at the end of second week and then plateau was observed in the 3rd
week. The continuous reduction of pain by gabapentin in our study may be explained on the basis of starting of gabapentin within 72 hours which may have had a role in reducing the pain provocation potential at receptor level and its anti-nociceptive properties.
The safety profile showed significantly more somnolence, dizziness, and gastro-intestinal side effects in dose of 900 mg/day as compared with 300 and 600 mg/day . This highlights that the dose of 600 mg/day is therapeutically more effective and a safe dose. The most common side effect was somnolence, but it was not a source of stress in our patients, rather nocturnal somnolence was perceived as mark of pain relief.
Geriatric patients usually are on multiple drugs for different medical and surgical conditions. A drug which has less drug interaction potential is therefore needed. Gabapentin, in all doses undergoes minimal metabolism, has minimal protein binding and is excreted unchanged by kidneys which accounts for its less drug interactions.[12
] As geriatric patients are at a higher risk to develop post herpetic neuralgia, gabapentin can be continued as single or combined therapy in cases of PHN.
The results of this study show that early initiation of gabapentin can be safe and effective alternative to analgesics and tricyclics in geriatric patients to reduce and prevent the pain in herpes zoster. Further trials can be done in future enrolling more number of patients with different combinations and different age groups to quantify the effect.