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Gary A. Mellick, D.O. American Pain Specialists, Inc. My RSD Sally Stauder Reflex sympathetic dystrophy has been my constant companion for the past two and one half years of my life. I fell on my basement steps on November 21, 1991 and since then my life was changed. Up until then I thought that being a college educator would be the most demanding challenge of my life. Little did I realize after six months and six physicians later, when I finally learned my diagnosis, that I was about to travel down a long, rocky road of pain and suffering, sleepless nights, crying and many hours of vigorous physical and occupational therapy to my arm, wrist, and hand. Following my diagnosis, my therapy consisted of stellate ganglion blocks, TENS unit therapy, repeated peripheral anesthetic nerve blocks, and a list of prescribed medications that barely took my pain away. A bone scan confirmed my dismay when the burning pain spread to my left arm. After being treated by Dr. Mellick for over one year, something miraculous happened to me on Friday, May 20, 1994, when I took my first gabapentin capsule at 5 PM. Within two hours after taking my first 300 mg capsule, I felt complete pain relief. This was followed by six hours of beautiful uninterrupted sleep and when I awoke, I was exhilarated over the magnitude of my pain relief! Of course, as with most medications, I experienced side effects. Initially these included euphoria, mild disorientation, dizziness, and drowsiness. They gradually resolved after several days. Later I experienced leg cramps, itching, and episodic diarrhea which disappeared. Nevertheless, the most amazing thing of all was that my pain racked body was now becoming less sensitive to light touch and by day ten of gabapentin therapy, I was able to hold my grand nephew in my arms for the first time (of course I cried). Finger movements had increased dramatically by day fifteen of therapy and occupational therapy was now much less painful and my myofascial treatments were more effective. Follow-up examinations with Dr. Gary Mellick showed that I had much less tenderness to touch and by one month after starting gabapentin, I was able to firmly shake hands with his office staff and experience no pain. My skin texture is normalizing, and my strength is gradually improving. Best of all, my family reports that I am now back to my former self. The awful depression has lifted and I am once again becoming an active participant in life. I am free at last. I am no longer a prisoner in my own body! Although I realize that not every one of you who read this will experience the same relief that this medication has afforded me, I still hope and pray that your response is as complete as mine. Thank God! At last there is hope for those of us who suffer with reflex sympathetic dystrophy. Gabapentin (Neurontin) u u u u u u u u An anticonvulsant introduced in February 1994. Indicated for treatment of partial seizures with or without secondary generalization. GABA-mimetic, crosses blood brain barrier Binds in outer cortex, hippocampus, etc. Receptor and biochemical function unknown Not protein bound, renal excretion Not metabolized by liver Benign efficacy-to-toxicity level Neurontin: Pain Management u Initial Clinical Experience – – u Reflex Sympathetic Dystrophy - May 20, 1994 Phobic Disorder Subsequent Clinical Experience – – – Acute & Chronic Pain Syndromes Cancer Pain Difficulty Initiating & Maintaining Sleep (DIMS) » With Pain » Without Pain Neurontin: Pain Management u Neuropathic Pain Syndromes u Visceral Pain Syndromes u Musculoskeletal Pain Syndromes MANAGEMENT OF PAINFUL PERIPHERAL NEUROPATHY WITH GABAPENTIN (NEURONTIN ) GABAPENTIN RELIEVES ABNORMAL PAINS IN A RAT MODEL OF PAINFUL PERIPHERAL NEUROPATHY: W.H. Xiao and G.L. Bennett*, Neurobiology and Anesthesiology Branch, NIDR, NIH, Bethesda, MD 20892 Gabapentin (1-(aminomethyl) cyclohexaneacetic acid; Neurontin ) is a cyclic GABA analog with an unique profile of anticonvulsant activity in animal models, an unique binding pattern in brain, and an unknown mechanism of action. An open label clinical trial (Mellick & Mellick, J. Pain Symptom Mgmt, 10:1-2, ‘95) of gabapentin in patients with reflex sympathetic dystrophy suggests that it may have efficacy in the treatment of painful peripheral neuropathies. Using rats with the chronic constriction injury (CCI) of Bennett & Xie (Pain, 33:87-107, ‘88) and an observer blinded as to drug condition, we have examined gabapentin’s effects on hyperalgesia and allodynia following (2, 4 and 24 hr) i.p. and lumbar intrathecal (i.t.) bolus injections on postoperative days 6-16 (at or near the period of peak symptom severity). Prior to drug administration, rats were shown to have statistically significant heat-hyperalgesia (paw withdrawal method), mechano-hyperalgesia (pin-prick test and mechanoallodynia (von Frey hair test). None of the i.p. and i.t. doses that we examined produced any obvious motor side-effects and none had any effect on the responses evoked from the sham-operated control side. In a dose-response trial of i.p. gabapentin (saline, 10, 25 and 75 mg/kg), heathyperalgesia and mechano-allodynia were significantly reduced in a doserelated manner for up to 4 hr. In an i.t. dose-response trial (saline, 7.5, 15, 37.5, and 75 mg; all 10 ml volume), heat-hyperalgesia was significantly reduced in a dose-related manner for up to 4 hr. An i.t. trial using 150 mg of gabapentin failed to reveal any efficacy against mechano-hyperalgesia; in the same animals this dose produced a significant suppression of heathyperalgesia and mechano-allodynia. Our results suggest that gabapentin may be useful in the clinical management of painful peripheral neuropathy and that its efficacy against heat-hyperalgesia and mechanoallodynia may be mediated largely or entirely by a spinal site of action. SOC. NEUROSCI. ABSTR., 21 (1995) IN PRESS Neurontin: Pain Management u Neuropathic Pain Syndromes – – – – – Peripheral Neuropathies/Neuralgias Phantom Limb & Stump Pain Herpes Zoster & Postherpetic Neuralgia Central Pain (MS, Stroke, Etc.) Complex Regional Pain Syndromes » Reflex Sympathetic Dystrophy (CRPS Type I) » Causalgia (CRPS Type II) Sympathetically Maintained Pain » Neurontin: Pain Management u Visceral Pain Syndromes – – – Lungs & Pleura Heart & Pericardium Abdomen » » » » » Pancreas, Liver, & Biliary System Chronic Pain After Surgery Stomach & Gastrointestinal Tract Kidney & Ureters Pelvis & Perineum Neurontin: Pain Management u Musculoskeletal Pain Syndromes – – – – Whiplash Injury Chronic Low Back Pain Fibromyalgia Restless Legs Syndrome & Periodic Limb Movement Disorder Neurontin: Pain Management u Restless Legs Syndrome – First described by Ekbom in 1945 – Characterized by: Irresistible leg movements, dysesthesia, worse in the evening and at bedtime. – Estimated prevalence of 5 to 10% of the population. – Familial incidence in 1/3 of cases (Boghen & Peyronnard, 1976) Restless Legs Syndrome PATIENTS TREATED WITH GABAPENTIN (NEURONTIN) Table 1 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. PT NAME A.W. B.E. F.L. G.E. M.L. N.B. P.S. S.J. S.C. S.J. W.L. B.J. D.M. D.G. W.L. H.D. AGE (YRS) 62 47 43 73 54 60 51 75 51 72 68 36 50 75 47 46 DURATION OF RLS 10 YRS 9 YRS 15 YRS 30 YRS 6 YRS 20 YRS 10 YRS 10 YRS 3 YRS 11 YRS 20 YRS 30 YRS 25 YRS 40 YRS 15 YRS >1 YRS NEURONTIN DOSE 400 PO TID 300 MG TID 400 5/D 300 MG BID 300 MG QHS 600 MG QHS 400 MG BID 400 MG BID 800 MG BID 800 MG QHS 300 MG TID 800 MG QHS 400 MG TID 400 MG 5/D 800 MG QHS 800 MG QHS RLS RELIEF 90% 75% 75% 100% 90% 50% 50% 90% 75% 100% 75% 95% 90% 80% 100% 100%