Understanding Sore Throat: Mechanisms, Pathophysiology, and Evidence-Based Treatments

Sore throat, clinically known as pharyngitis, represents a common inflammatory condition characterized by pain, irritation, and discomfort in the throat. This comprehensive analysis explores the underlying mechanisms through which throat pain manifests, from neural transduction pathways to inflammatory cascades involving neutrophil activation and cytokine release. Current evidence strongly supports several treatment options including low-dose corticosteroids, which can reduce pain within 24 hours, and topical non-steroidal anti-inflammatory drugs like flurbiprofen and benzydamine hydrochloride that provide targeted relief without systemic side effects. Less substantiated approaches include various ethnobotanical remedies and homeopathic treatments, which lack robust clinical validation despite traditional usage. Understanding the mechanistic complexity of sore throat enables more precise and effective therapeutic interventions beyond inappropriate antibiotic prescriptions that contribute to antimicrobial resistance.

Definition and Etiology of Sore Throat

Sore throat, medically termed pharyngitis, is defined as pain, inflammation, or irritation affecting the pharynx and surrounding tissues. This common condition can manifest across various clinical contexts including as a symptom of acute upper respiratory tract infections, a postoperative complication following endotracheal intubation, or as part of the symptom complex in systemic infections such as COVID-19. The etiology of sore throat is multifactorial, encompassing infectious causes (viral and bacterial pathogens), physical trauma (such as from intubation or endotracheal tubes), environmental irritants, and non-infectious factors that collectively contribute to throat inflammation and subsequent pain sensation. Despite its frequent occurrence, sore throat represents a significant burden on healthcare systems worldwide, often leading to physician consultations, lost productivity, and inappropriate antibiotic prescriptions. Understanding the precise mechanisms underlying throat pain is essential for developing targeted therapeutic approaches that address the specific pathophysiological processes rather than merely providing symptomatic relief without addressing the underlying cause213.

The categorization of sore throat often depends on its duration and pathogenesis, with acute pharyngitis typically resolving within days to weeks, while chronic forms may persist for extended periods. Viral etiologies account for approximately 70-85% of acute pharyngitis cases in adults, with rhinovirus, coronavirus, adenovirus, and influenza virus being common culprits. Bacterial causes, predominantly group A beta-hemolytic streptococcus (GABHS), represent about 5-15% of adult cases, though this percentage is higher in pediatric populations. While viral and bacterial infections constitute the majority of sore throat cases, the pathophysiology extends beyond mere pathogen presence to include complex host immune responses, neurogenic inflammation, and molecular signaling pathways that collectively produce the clinical manifestation of throat pain1013. Non-infectious factors including allergies, environmental pollutants, smoking, alcohol consumption, vocal strain, and acid reflux also contribute significantly to the development of pharyngeal inflammation and subsequent symptomatology in susceptible individuals1216.

Pathophysiological Mechanisms of Sore Throat

The pathophysiology of sore throat involves complex interactions between epithelial damage, immune cell activation, inflammatory mediator release, and neural signaling. In endotracheal tube-induced sore throat, mechanical trauma to the pharyngeal and laryngeal mucosa triggers a sterile inflammatory response characterized by neutrophil infiltration and activation. These activated neutrophils release elastase, reactive oxygen species, and proinflammatory cytokines that directly contribute to nociceptive stimulation and tissue damage. Research has demonstrated that this process is coupled with the release of mitochondrial DNA (mtDNA), which functions as a damage-associated molecular pattern (DAMP) that further propagates inflammation through Toll-like receptor 9 (TLR9)-dependent mechanisms1. This creates a self-perpetuating inflammatory cascade where mtDNA release stimulates additional neutrophil activation, creating a cycle of inflammation and pain that persists even after the initial insult has been removed.

In infectious pharyngitis, pathogen invasion of the pharyngeal mucosa initiates a different but overlapping inflammatory response. Viral pathogens directly infect and damage epithelial cells, triggering the release of interferons, interleukins, and other cytokines that recruit immune cells to the site of infection. Bacterial pathogens, particularly group A streptococcus, produce exotoxins and stimulate robust neutrophilic infiltration, often resulting in more severe inflammation than viral causes. The immune response, while necessary for pathogen clearance, contributes significantly to symptomatic manifestations through local tissue edema, hyperemia, and direct stimulation of nociceptive nerve endings in the pharyngeal region. These inflammatory processes activate peripheral nociceptors that transmit pain signals to the central nervous system, resulting in the conscious perception of throat pain and discomfort12. Regardless of the initial trigger, once established, the inflammatory response in the pharyngeal mucosa follows similar molecular pathways involving pro-inflammatory cytokine production, immune cell recruitment, and neurogenic inflammation.

COVID-19-associated sore throat demonstrates yet another mechanistic pathway, where SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) receptors to gain cellular entry. The virus then hijacks the cell's transcriptional machinery for viral replication and assembly, leading to direct cytopathic effects and subsequent inflammation. The throat pain in COVID-19 results from both direct viral damage to pharyngeal tissues and the immune system's response to viral invasion, which includes the release of inflammatory mediators that sensitize pain receptors. This complex interplay between viral pathogenesis and host response creates the characteristic sore throat frequently reported as an early symptom of COVID-19 infection, with molecular studies suggesting distinctive inflammatory patterns compared to other viral causes of pharyngitis61820.

Neural Mechanisms and Nociceptor Involvement

The sensation of throat pain involves sophisticated neural transduction pathways mediated primarily through specialized ion channels expressed on sensory neurons. Transient receptor potential (TRP) channels represent a superfamily of non-selective cation channels that function as polymodal sensors and play a critical role in nociception throughout the body, including the pharyngeal region. Five specific TRP channels—TRPV1, TRPV4, TRPM3, TRPM8, and TRPA1—are particularly relevant to sore throat pathophysiology as they are expressed on peripheral ganglia and nerves that innervate the pharyngeal mucosa. These channels respond to various stimuli including temperature changes, mechanical distortion, and chemical mediators released during inflammation, transducing these stimuli into electrical signals that propagate to the central nervous system8. The activation of TRP channels during pharyngeal inflammation represents a critical step in the pain pathway, as these channels regulate cation influx (particularly calcium) that triggers action potential generation and subsequent pain signaling.

TRPV1 (the vanilloid receptor) responds to heat, acid, and various inflammatory mediators, making it particularly relevant in the context of inflammatory pharyngitis. TRPA1 channels react to irritants and endogenous inflammatory compounds, while TRPM8 is activated by cooling compounds and moderate cold temperatures—explaining why cold therapies such as ice chips or cold beverages may temporarily alleviate sore throat pain. These neural mechanisms establish a molecular basis for both the sensation of pain and the effectiveness of certain analgesic interventions targeting these specific receptors. Beyond simple nociception, activation of these neural TRP channels enables complex crosstalk between neurons, immune cells, and epithelial cells, creating an integrated network that regulates inflammatory responses in the throat810. This neuro-immune interaction explains why neurally targeted therapies such as local anesthetics and certain anti-inflammatory compounds can effectively reduce both pain sensation and the underlying inflammatory processes simultaneously.

The mechanism of ice therapy for post-tonsillectomy pain further illuminates the role of these receptors in throat pain. Cold temperatures activate TRPM8 channels while simultaneously inhibiting TRPV1 activity, effectively reducing pain signal transmission10. This dual mechanism explains the rapid but temporary relief provided by cold therapies in the context of throat pain. Furthermore, neurogenic inflammation—where activated sensory neurons release neuropeptides such as substance P and calcitonin gene-related peptide that promote vasodilation and plasma extravasation—contributes significantly to the inflammatory component of sore throat. Understanding these neural mechanisms provides a theoretical framework for developing targeted therapies that modulate specific receptors involved in throat pain sensation rather than broadly suppressing inflammation or providing systemic analgesia38.

Inflammatory Pathways and Cytokine Networks

The inflammatory component of sore throat involves complex cytokine networks and cellular interactions that amplify and sustain the painful condition. In endotracheal tube-induced sore throat, neutrophil recruitment and activation represent a primary driver of inflammation. These neutrophils demonstrate elevated adhesion molecule expression, increased TLR9 expression, and constitutive reactive oxygen species generation. The accumulation of mitochondrial DNA in tracheal lavage fluid stimulates neutrophils to release mediators associated with pain in a TLR9-dependent manner, establishing a clear mechanistic link between cellular damage, neutrophil activation, and pain perception1. This pathway represents a non-infectious inflammatory cascade triggered by mechanical trauma rather than pathogen invasion, yet resulting in similar symptomatic manifestations through convergent inflammatory mechanisms.

Proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and various chemokines coordinate the inflammatory response in the pharyngeal tissues regardless of the initial trigger. These molecular mediators increase vascular permeability, promote immune cell recruitment, and directly sensitize nociceptors, thereby lowering the threshold for pain perception. Additionally, inflammatory processes drive local tissue edema that physically compresses nerve endings and further contributes to pain sensation. Studies of postoperative sore throat reveal that the severity of symptoms correlates with the concentration of these inflammatory mediators in tracheal secretions, establishing a quantitative relationship between inflammatory intensity and clinical manifestations19. The self-perpetuating nature of these inflammatory pathways explains why sore throat symptoms often persist for days even after the initial trigger has resolved, as the inflammatory cascade continues independently until actively resolved through intrinsic anti-inflammatory mechanisms or therapeutic intervention.

Inflammation of the pharyngeal mucosa also involves mast cell degranulation and histamine release, contributing to localized vasodilation, tissue edema, and nerve sensitization. The sensitization of peripheral nociceptors by inflammatory mediators represents a form of peripheral sensitization where normally non-painful stimuli (such as swallowing) become painful—a phenomenon known as allodynia. This explains why activities that normally do not cause discomfort, such as speaking or eating, become painful during episodes of pharyngitis. The complex interplay between immune cells, structural cells of the pharyngeal mucosa, and sensory neurons creates an integrated inflammatory-nociceptive network that manifests clinically as throat pain, swelling, and functional impairment8. Understanding these molecular pathways provides rationale for anti-inflammatory therapeutic approaches targeting specific cytokines or cellular components of the inflammatory response rather than broadly suppressing all inflammatory processes.

Evidence-Based Treatments for Sore Throat

Corticosteroids represent one of the most thoroughly researched and effective interventions for sore throat management, particularly in acute cases. Systematic reviews and meta-analyses demonstrate that single low-dose corticosteroids, such as oral dexamethasone (maximum 10 mg), double the likelihood of experiencing pain relief within 24 hours compared to placebo (relative risk 2.2, 95% confidence interval 1.2 to 4.3). In emergency department settings, corticosteroids reduce pain intensity by 1-2 points on an 11-point scale at 12 hours post-administration11. The mechanism of action involves potent anti-inflammatory effects through inhibition of multiple inflammatory pathways, reduced cytokine production, and decreased immune cell activation and recruitment. When administered alongside antibiotics for acute pharyngitis, corticosteroids accelerate pain relief by approximately 6 hours, providing meaningful improvement in patient comfort19. For postoperative sore throat prevention, nebulized corticosteroids consistently rank as the most effective intervention among various nebulized pharmacological agents, highlighting their versatility across different sore throat etiologies9. While concerns exist regarding potential adverse effects of corticosteroids, the short-term, low-dose regimens typically employed for sore throat management demonstrate favorable safety profiles with minimal clinically significant complications.

Non-steroidal anti-inflammatory drugs (NSAIDs), particularly topical formulations, offer targeted relief with minimized systemic exposure. Flurbiprofen 8.75 mg, delivered locally as lozenges, sprays, or microgranules, demonstrates well-documented efficacy for acute pharyngitis. Clinical studies indicate that this intervention provides rapid onset and prolonged symptomatic relief from throat pain, sensation of swollen throat, and difficulty swallowing13. The local delivery method ensures high concentration at the site of inflammation while limiting systemic absorption and associated side effects. Benzydamine hydrochloride, a topical indolic NSAID with unique pharmacological properties, combines analgesic, anesthetic, anti-inflammatory, and antimicrobial activities. Unlike conventional NSAIDs, benzydamine does not inhibit cyclooxygenase or lipoxygenase enzymes but instead stabilizes cell membranes, inhibits pro-inflammatory cytokine production, and interacts with cationic channels to produce local anesthesia. This multifaceted mechanism makes it particularly suitable for sore throat management, where pain, inflammation, and potential microbial colonization coexist515. Both flurbiprofen and benzydamine represent evidence-based topical interventions that directly target the site of inflammation without significant systemic effects, aligning with current recommendations for symptomatic management of acute sore throat.

Simple analgesics such as paracetamol (acetaminophen) provide symptomatic relief through central pain modulation and modest peripheral anti-inflammatory effects. While less potent than NSAIDs for inflammatory conditions, paracetamol offers a favorable safety profile, particularly for patients with contraindications to NSAIDs such as gastric ulceration, renal impairment, or aspirin-sensitive asthma. Clinical consensus recommends paracetamol as a first-line analgesic option for symptomatic management of acute sore throat, particularly in pediatric populations and patients with comorbidities2. For postoperative sore throat prevention and treatment, nebulized magnesium and ketamine demonstrate efficacy comparable to corticosteroids in some studies, though with less consistent evidence. These agents act through different mechanisms—magnesium through calcium antagonism and NMDA receptor modulation, and ketamine through NMDA receptor antagonism—providing alternative options for patients unsuitable for corticosteroid or NSAID therapy9. The diverse pharmacological approaches to sore throat management reflect the complex pathophysiology involving multiple cellular, molecular, and neural pathways that collectively manifest as throat pain and inflammation.

Treatments with Limited or Controversial Evidence

Antibiotics remain one of the most controversial interventions for sore throat management, with substantial evidence indicating inappropriate overprescription. Despite guidelines recommending symptomatic management as first-line treatment for most sore throat cases, antibiotics continue to be prescribed at high rates, contributing to the global crisis of antimicrobial resistance. The vast majority of sore throat cases (70-85%) have viral etiologies unresponsive to antibiotic therapy, and even bacterial pharyngitis often resolves spontaneously without complications213. Current evidence suggests that antibiotic therapy should be reserved for high-risk patients or those with clear evidence of bacterial infection, particularly group A streptococcal pharyngitis with risk factors for complications. The indiscriminate use of antibiotics for sore throat not only contributes to antimicrobial resistance but also exposes patients to potential adverse effects without meaningful clinical benefit in most cases. Improved diagnostic tools, such as the McIsaac score for streptococcal pharyngitis, can help clinicians make more informed decisions regarding antibiotic prescribing, reducing unnecessary treatments while ensuring appropriate therapy for those who genuinely require it2.

Ethnobotanical and traditional medicine approaches for sore throat represent a vast collection of practices with varying levels of scientific validation. Iranian traditional medicine employs numerous medicinal plants including Artemisia, pumpkin, Quarcus brantii, Solanum nigrum, Mentha pulegium, sage, eucalyptus, and cannabis for treating throat pain and ear discomfort. While these remedies have historical precedence and cultural significance, most lack rigorous clinical evaluation through randomized controlled trials or systematic reviews4. The therapeutic potential of these botanical agents likely stems from naturally occurring compounds with anti-inflammatory, analgesic, or antimicrobial properties, yet standardization issues, dosage variability, and insufficient safety data limit their integration into evidence-based practice. Nevertheless, ethnobotanical approaches continue to influence contemporary pharmaceutical development, with many modern drugs originating from traditional botanical remedies, suggesting potential for discovering novel therapeutic agents for sore throat management through systematic investigation of traditional practices.

Homeopathic interventions represent another category with limited scientific support despite anecdotal reports of efficacy. A case report describes successful treatment of postoperative sore throat, hoarseness, and aphonia using Arnica montana 200CH, with three doses administered over 36 hours producing significant symptom improvement within 48 hours17. However, such isolated reports provide insufficient evidence to establish efficacy by contemporary scientific standards, and the proposed mechanisms—involving extreme dilutions beyond Avogadro's number—conflict with established physical and chemical principles. Despite these limitations, homeopathic remedies maintain popularity in certain populations, highlighting the gap between scientific consensus and public health practices. The persistence of such approaches despite limited empirical support underscores the importance of comprehensive patient education, shared decision-making, and integration of patient preferences with best available evidence when managing common conditions like sore throat in clinical practice.

Conclusion

Sore throat represents a complex clinical entity with multifaceted pathophysiology involving intricate interactions between physical tissue damage, immune system activation, inflammatory cascades, and neural signaling mechanisms. The diverse etiologies—ranging from infectious pathogens to mechanical trauma and environmental irritants—converge on common inflammatory pathways that ultimately result in the clinical manifestation of throat pain and discomfort. Transient receptor potential channels, particularly TRPV1, TRPA1, and TRPM8, play crucial roles in the neural transduction of painful stimuli, while inflammatory mediators including mitochondrial DNA, pro-inflammatory cytokines, and reactive oxygen species orchestrate the immune response that amplifies and sustains the painful condition. This mechanistic understanding provides the theoretical foundation for targeted therapeutic interventions that address specific components of the pathophysiological process rather than merely providing symptomatic relief.

Current evidence strongly supports several treatment approaches for sore throat management, with corticosteroids and topical NSAIDs demonstrating the most robust efficacy data. Single low-dose corticosteroids effectively reduce pain intensity and accelerate recovery in acute pharyngitis, while topical NSAIDs such as flurbiprofen and benzydamine provide targeted relief with minimal systemic effects. Simple analgesics including paracetamol offer safe symptomatic management for milder cases or patients with contraindications to other therapies. In contrast, antibiotics show limited benefit for most sore throat cases and contribute to antimicrobial resistance when prescribed inappropriately, highlighting the importance of judicious prescribing based on accurate diagnosis. Traditional and complementary approaches, including ethnobotanical remedies and homeopathic interventions, lack robust scientific validation despite historical usage and anecdotal reports of efficacy, emphasizing the need for rigorous evaluation before integration into evidence-based practice.

The evolving understanding of sore throat pathophysiology continues to inform therapeutic innovation and clinical practice guidelines. Future directions may include targeted modulation of specific TRP channels, precision inhibition of key inflammatory mediators, and development of novel locally-delivered agents that provide pain relief while addressing underlying pathophysiological processes. By aligning treatment approaches with mechanistic insights, clinicians can provide more effective management of this common but impactful condition, improving patient outcomes while minimizing unnecessary interventions and their associated risks. This integrated approach—combining scientific understanding with evidence-based therapeutic selection—represents the optimal strategy for addressing the significant individual and public health burden of sore throat across diverse clinical contexts.