Though stress is an integrated part of the modern life, defining stress in biological systems is difficult. Anxiety, medication, metabolic disorder, neuro-endocrinological abnormalities, immunological responses, neuro-immune interaction and several other internal and external factors are important which induce stress and pain in higher organisms. Stress and pain are often synonymous and overlapping to a large extent, but these two responses are different at the behavioral, cellular and molecular levels. Importance of Transient Receptor Potential (TRP) group of non-selective cation channels in the development and regulation of different forms of pain is well established. However, recent studies confirmed that TRPs can regulate neuroplastic changes through neuro-endocrine signaling, neuro-immune interactions and psychological state variables suggesting that abnormalities in TRP-signaling can indeed affect the hypothalamic-pituitary-adrenal (HPA) axis and several other metabolic pathways and thus may generate stress at various levels. Therefore, TRPs are important factors that can link stress with pain. This review summarizes the role of TRPs, their effects and clinical implications in the context of different types of pain which can be relevant for stress too.