Disclosed are compositions for treatment of pain comprising a first compound and a second compound, the first compound is an opioid antagonist that treats pain by blocking Toll-like receptor 4 (TLR4) and the second compound is a cyclooxygenase (COX) inhibitor that enhances the pain treatment effect of the first compound. Examples of opioid antagonist include naltrexone and naloxone. Examples of cyclooxygenase inhibitors include ibuprofen, naproxen, meloxicam, diclofenac and meclofenamic acid, synergistic pharmaceutical compositions thereof, and their use in the treatment, prevention, and reversal of neuropathic pain and nociceptive pain with an allodynic component.