The purpose of the study is to investigate the clinical benefit of tramadol/acetaminophen versus non-steroidal anti-inflammatory drugs (NSAID) (diclofenac 50 milligram [mg]) in the treatment of pain in participants with ankylosing spondylitis (inflammation of the spine causing pain and stiffness) receiving stable treatment of disease modifying anti-rheumatic drugs (DMARDs).

This is a single center, open labeled (all people know the identity of intervention), randomized (study drug assigned by chance), parallel group (a medical research study comparing the response in two or more groups of participants receiving different interventions (treatments) trial to compare the effectiveness (pain relief) and safety of tramadol 37.5 mg and acetaminophen 325 mg with diclofenac in participants with ankylosing spondylitis receiving stable treatment of disease modifying anti-rheumatic drugs (DMARDs). Participants who meet the eligibility criteria will be randomized to one of the two treatment groups (tramadol/acetaminophen and Diclofenac). One group will be treated with tramadol 37.5 mg/acetaminophen 325 mg combination tablet and another group will be treated with diclofenac 50 mg tablet. Participants randomized into this study will be instructed to take one tablet Ultracet or diclofenac 50 mg orally, twice a day for 8 weeks. Evaluations will be performed as outlined: at Screening, at Baseline, and at Weeks 2, 4, and 8. The primary efficacy parameter is to compare the mean change from Baseline in visual analogue scale (VAS) pain score between the two treatment groups (tramadol/acetaminophen versus diclofenac). Participants' safety will be monitored throughout the study.

Inclusion Criteria:

• Diagnosis of ankylosing spondylitis (AS), as defined by Modified New York Criteria for ankylosing spondylitis: a) Low-back pain of at least 3 months duration improved by exercise and not relieved by rest b) Limitation of lumbar spine in sagittal and frontal planes c) Chest expansion decreased relative to normal values for age and sex d) Bilateral sacroiliitis, grade 2-4 or Unilateral sacroiliitis, grade 3-4 (Stoke)
• Participants are suffering from pain, with visual analogue scale (VAS) pain score greater than or equal to (>=) 40 millimeter (mm)
• Participants are receiving disease modifying anti-rheumatic drugs (DMARDs), which have reached to the stable dosage within 4 weeks prior to the randomization visit - Serum creatinine less than or equal to (<=) 1.2 milligram per deciliter (mg/dL)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 times the laboratory's upper limit of normal
• Exclusion Criteria:
• Had an inadequate response to tramadol hydrochloride (HCl) therapy, or have discontinued tramadol HCl therapy due to adverse events
• Have taken tramadol HCl within 4 weeks prior to the entry of the study
• Have taken other medications for pain relief within 4 weeks prior to the entry of the study, except rescue medications
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders
• Women with pregnancy or breast-feeding