The Science of Carpal Tunnel Syndrome

Carpal tunnel syndrome (CTS) is a peripheral nerve compression neuropathy resulting from increased pressure on the median nerve as it passes through the carpal tunnel at the wrist. The carpal tunnel is an anatomically confined space bounded by carpal bones dorsally and the transverse carpal ligament (flexor retinaculum) volarly. Nine flexor tendons (four flexor digitorum superficialis, four flexor digitorum profundus, and flexor pollicis longus) pass through this tunnel alongside the median nerve, creating potential for compression when tunnel pressure exceeds capillary perfusion pressure (30 mmHg). The pathophysiological cascade begins with mechanical compression causing impaired microvascular blood flow to the nerve (ischemia) and reduced venous drainage (congestion). This leads to nerve edema, further increasing tunnel pressure in a vicious cycle. Initially, compression affects the myelin sheath causing focal demyelination at the compression site, manifesting as intermittent paresthesias and nocturnal symptoms. With sustained compression, axonal degeneration develops, progressing from distal sensory fibers to motor fibers, eventually causing permanent sensory loss and thenar muscle atrophy if untreated. Multiple factors contribute to increased carpal tunnel pressure. Tenosynovitis (inflammation of the tendon sheaths) from repetitive motion increases the volume of contents within the fixed-space tunnel. Systemic conditions including pregnancy (fluid retention), hypothyroidism (myxedematous tissue accumulation), rheumatoid arthritis (synovial inflammation), diabetes mellitus (metabolic factors affecting nerves), and obesity (increased tissue pressure) predispose to CTS. Anatomical variations such as persistent median artery, aberrant muscles within the tunnel, or smaller tunnel dimensions increase baseline pressure. Wrist position dramatically affects tunnel pressure - wrist flexion increases pressure to 90 mmHg while extension increases it to 110 mmHg compared to 32 mmHg in neutral position. The median nerve provides sensory innervation to the palmar aspect of the thumb, index, middle, and radial half of the ring finger, plus motor innervation to the thenar muscles (abductor pollicis brevis, opponens pollicis, superficial head of flexor pollicis brevis) responsible for thumb opposition and abduction. This explains the characteristic sensory distribution and eventual thumb weakness in advanced CTS. The condition often coexists with cervical radiculopathy, thoracic outlet syndrome, or pronator syndrome (double or triple crush phenomenon), where proximal nerve compression makes distal compression sites more symptomatic. Risk factors include female gender (3:1 ratio, likely due to smaller tunnel anatomy and hormonal influences), age 40-60 years (peak incidence), pregnancy (third trimester fluid retention), obesity (BMI greater than 29), diabetes mellitus (2-3 times higher prevalence), hypothyroidism, rheumatoid arthritis, wrist trauma or fracture history, and occupations requiring repetitive forceful gripping, sustained wrist flexion/extension, or vibration exposure (assembly line work, meat processing, construction, computer-intensive work).