Inflammation and pain: a brief review of mechanisms and therapeutics

Abstract

Inflammation is a complex immunological response to harmful stimuli such as pathogens, damaged cells, and toxins, playing a fundamental role in host defense and tissue repair. This narrative review selected 41 recent studies addressing the cellular, molecular, and pathophysiological mechanisms of inflammation and its relationship with pain, including lifestyle influences and current and emerging therapeutic strategies. Acute inflammation is characterized by rapid onset, vasodilation, increased vascular permeability, and predominant neutrophil recruitment, with mediators such as prostaglandins, leukotrienes, histamine, bradykinin, and pro-inflammatory cytokines, and may generate systemic manifestations such as peripheral and pulmonary edema. Chronic inflammation results from failure of resolution, with persistent mononuclear infiltrate, tissue remodeling, fibrosis, and activation of the adaptive immune response. Inflammatory pain arises from peripheral sensitization of nociceptors and central activation, mediated by excitatory neurotransmitters, ion channels, and specific receptors, favoring hyperalgesia and chronification. Active resolution, promoted by lipoxins, resolvins, and maresins, modulates inflammation and nociception. Therapeutic interventions include nonsteroidal anti-inflammatory drugs, glucocorticoids, biological therapies, and JAK/STAT inhibitors; however, their adverse effects highlight the need for safer novel approaches. Lifestyle factors such as obesity, chronic stress, and physical inactivity contribute to low-grade inflammation and persistent pain. Understanding these interactions is crucial for the development of integrated strategies that reconcile anti-inflammatory and analgesic efficacy with clinical safety.