Is irritable bowel syndrome (IBS) associated with neuropathic, visceral, or nociceptive pain?

Pain Classification in Irritable Bowel Syndrome

IBS is characterized by visceral pain with features of both peripheral and central sensitization, not neuropathic pain. The pain arises from hypersensitive visceral afferents and altered central processing of gut signals, affecting 20-60% of patients with enhanced perception to normal gut stimuli 1.

Primary Pain Mechanism: Visceral Hypersensitivity

The predominant pain mechanism in IBS is visceral hypersensitivity with both peripheral and central sensitization components, not classic neuropathic pain from nerve damage 1, 2.

Peripheral Sensitization

• Inflammatory mediators (prostaglandins, leukotrienes, serotonin, histamine, cytokines) directly act on nociceptor terminals in the gut, upregulating their sensitivity and excitability 1, 2
• This creates primary hyperalgesia (increased sensitivity to painful stimuli) and allodynia (non-painful stimuli perceived as painful) at the gut level 1
• Between 6-17% of IBS patients develop symptoms following gastroenteritis, with increased mucosal T lymphocytes altering the environment around nerve terminals 1, 2
• Activated mast cells cluster near nerve endings in the gut mucosa, with pain severity correlating directly with this proximity 1, 2

Central Sensitization

• Increased excitability of spinal neurons amplifies pain signals from both nociceptive and non-nociceptive inputs, creating secondary hyperalgesia in surrounding uninjured tissue 1, 2
• IBS patients demonstrate greater radiation of pain to somatic structures during colonic stimulation compared to healthy individuals 1, 2
• Some IBS patients develop fibromyalgia (characterized by somatic hyperalgesia), demonstrating that sensitization extends beyond the gut through viscero-somatic convergence at the spinal cord level 1
• Hypersensitivity often extends to more proximal gut regions due to overlapping innervation patterns 1

Why Not Neuropathic Pain

IBS pain lacks the hallmark features of true neuropathic pain (burning, shooting, electric-like sensations from nerve damage), instead presenting as visceral discomfort with altered gut perception 1.

• The pain originates from hypersensitive but structurally intact visceral afferents responding to normal gut stimuli, not from damaged nerves 1
• Approximately 90% of high-amplitude propagating contractions coincide with abdominal pain or cramps, demonstrating the visceral-motor correlation 1, 2
• The pain is characteristically diffuse, poorly localized, and associated with altered bowel habits—classic visceral pain features 1

Central Pain Processing Alterations

Beyond peripheral mechanisms, IBS involves complex alterations in brain processing of visceral signals 1.

• Functional brain imaging demonstrates visceral sensation representation in primary (S1) and secondary somatosensory cortex (S2), mediating sensory discriminative aspects 1
• Stronger representation occurs in paralimbic and limbic structures (anterior insula, anterior cingulate, prefrontal cortices) that mediate affective and cognitive pain components 1
• Subcortical regions (thalamus, periaqueductal grey matter) show altered activation patterns in response to gut stimulation 1
• Dysregulation of the brain-gut axis involves altered perception and modulation of visceral afferent signals, with greater stress-reactivity 1

Autonomic Nervous System Dysfunction

Autonomic dysregulation contributes to pain generation through altered gut function 1, 2.

• Reduction in parasympathetic activity combined with increased sympathetic nervous system activity is consistently observed 1, 2
• Reduced vagal tone impacts gut motility, visceral sensitivity, peripheral inflammation, and gut permeability 1, 2

Clinical Implications

Understanding IBS as visceral hypersensitivity rather than neuropathic pain guides treatment selection 1.

• Treatments targeting visceral hypersensitivity (neuromodulators, gut-directed therapies) are more appropriate than those for neuropathic pain 1
• Centrally acting drugs targeting brain regions responsive to pain and stress may be more effective than peripheral neuropathic pain medications 1
• The hypersensitive gut with enhanced visceral perception represents one of three interrelated pathophysiological factors, alongside altered gut reactivity and brain-gut axis dysregulation 1

Common Pitfall to Avoid

Do not misclassify IBS pain as neuropathic simply because central sensitization is present—central sensitization occurs in visceral pain syndromes without constituting true neuropathic pain from nerve damage 1, 2.