Study Design Prospective cohort study. Objective Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP) and nociceptive (NoP) low back pain. Traditionally NeP and NoP have been primarily attributed to patho-anatomical abnormalities within the lumbar spine. However, increasing evidence points to multifaceted involvement, encompassing a range of physical, biomechanical, chemical, and psychosocial factors. The study aimed to determine the independent relationship between NeP as assessed by the PainDETECT questionnaire and non-spinal comorbid medical conditions. Methods A prospective cohort study was conducted involving 400 patients suffering from chronic LBP (>6months), aged >18 years, who complete the PainDETECT questionnaire and provided responses regarding the presence of any comorbid conditions. A binary logistic regression model was used to analyse the confounding status of comorbid medical conditions and pain severity measured by NRS to determine independent relationships between specific conditions and neuropathic pain. Results The study included 143 and 257 patients suffering from NeP and NoP, respectively. The NeP group had a 38% higher mean numerical rating scale score compared to the NoP group (8.10 [Formula: see text] 1.55 vs 5.86[Formula: see text] 2.26, P < 0.001). The odds of developing NeP were 2.9 Exp(B) = 2.844, 95%C.I. [1.426-5.670], P < 0.01), 2.7 (Exp(B) = 2.726, 95%C.I. [1.183-6.283], P < 0.05) and 2.8 (Exp(B) = 2.847, 95%C.I. [1.473-5.503], P < 0.05) times higher in patients suffering from gastrointestinal conditions, rheumatoid arthritis, and depression, respectively. Conclusion NeP as determined by the PainDETECT questionnaire, is associated with gastrointestinal conditions, rheumatoid arthritis, and depression. This pioneering study has shed light on the potential involvement of the gut microbiome as a common factor connecting non-spinal comorbidities and NeP. These findings underscore the importance of formulating personalized management plans tailored to individual pain and medical profiles, rather than relying on a blanket approach to pain management.