This study is a randomized, open-label multi-center evaluation of the tolerability of treatment with NGX-4010 in conjunction with pre-patch topical application of one of three 4% lidocaine-based local anesthetic products. Eligible subjects will have moderate to severe neuropathic pain secondary to painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN) or HIV-associated neuropathy (HIV-AN), with average numeric pain rating scale (NPRS) scores during screening of 3 to 8 (inclusive).

Key Eligibility Criteria:

• Must have had for at least 3 months painful diabetic neuropathy, or postherpetic neuralgia, or painful HIV-associated neuropathy, with moderate to severe pain on average.
• Must not have significant pain due to other causes (for example, arthritis).
• Must have intact skin at the treatment area.
• Must be prepared to remain on the same pain medications at the same doses as before the study for the entire duration of the study (12 weeks).
• Must not use topical pain medications on painful areas.
• Must be able to comply with study requirements such as completing daily pain diary and attending study visits and refrain from extensive travel during study participation.
• Must be at least 18 years old, not pregnant, and able to take care of self independently, with only occasional assistance if needed.
• No significant medical problems of the heart, kidneys, liver or lungs, or cancer.
• No history or current problem with substance abuse.