• Tolerability (e.g., number of adverse effects, number of drop-outs)
• Safety (i.e., number of serious adverse events)
• Brief Pain Inventory interference items
• Daily diary sleep interference ratings
• Beck Depression Inventory
• Short-form Health Survey 36 (SF-36)
• Short-Form McGill Pain Questionnaire
• Patient Global Impression of Change scale
• Kurtzke Expanded Disability Status Scale

This study will determine whether treatment with an extended-release opioid or topical lidocaine is effective in relieving distal symmetric lower extremity burning pain associated with multiple sclerosis (MS). If treatment with topical lidocaine is efficacious, it will have important implications for understanding this chronic pain syndrome, which is widely assumed to be caused by central nervous system pathology.

This study is a single-center, double-blind, 15-week, 3-period crossover clinical trial. Subjects will complete each of the following 5-week long periods (unless they withdraw from the trial): 1) placebo pills and topical lidocaine patches, 2)extended-release oxycodone pills and placebo(vehicle) patches, and 3)placebo pills and placebo patches. Sixty subjects will be randomized to one of 6 treatment sequences. It is expected that this trial will take approximately 2 years to complete.

• Neuropathic Pain
• Chronic Pain
• Multiple Sclerosis

• Drug: Lidocaine patch 5%
• Drug: Extended-release oxycodone
• Drug: Placebo extended-release oxycodone pills
• Drug: Placebo lidocaine patches

Inclusion Criteria:

• "Definite MS" as defined by revised McDonald criteria.
• Bilateral distal symmetric burning pain involving both feet for at least three months.
• Baseline weekly average pain rating equal to four or greater on 0-10 numerical scale.
• Stable MS medication and pain-related medications for 8 weeks prior to screening.
• Must come to Research Center for appointments

Exclusion Criteria:

• Topical treatment with lidocaine, capsaicin, or other topical analgesics within 3 months prior to screening.
• Any treatment with opioid analgesics or tramadol within 3 months prior to screening.
• Hypersensitivity to Lidoderm, lidocaine, or other local anesthetics.
• Hypersensitivity or inability to tolerate opioid analgesics.
• Current treatment with a total of 3 or more antidepressant or anticonvulsant drugs for pain.
• Current treatment with Class I anti-arrhythmic agents at baseline.
• Beck Depression Inventory score > 16 or clinically significant depression or dementia.
• History of suicide attempt or current intent or plan.
• History of excessive alcohol use or any illicit drug use within the past 2 years.
• Lack of adequate birth control in pre-menopausal women of childbearing age.
• Other pain more severe than lower extremity burning pain.
• Open skin lesions in the area where the lidocaine patch is to be applied.
• Cancer within the previous 5 years other than skin cancer.
• MS exacerbation or any treatment with corticosteroids within 3 months prior to screening.
• History of peripheral neuropathy, lower limb amputation, or another neuromuscular syndrome or systemic disorder known to be associated with sensory neuropathy.
• Does not meet criteria of baseline lab values at screening visit.
• Nerve conduction studies consistent with peripheral neuropathy.