MiR-155 and its functional variant rs767649 contribute to the susceptibility and survival of hepatocellular carcinoma
inflammation sensitises nociceptors, as we saw above, should our treatment target nociceptiors in IBS? Intuitively, feeling pain should be related to sensing noxious stimuli. However, nociceptor activation does not equate pain perception. For example, spinal anaesthesia blocks acute pain without affecting nociceptor activation. Conversely, visceral pain and the correlated activation of brain structures involved in pain perception can be seen without any afferent input from the organ structure (eg, Song et al). Listening to IBS patients, we typically hear about several different sensations, such as bloating, distension, cramps, urgency or a vague uneasiness, all of which are part of the overall burden of disease, but are not easily accounted for by sensitisation of high threshold nociceptors. Detailed psychophysical experiments in IBS patients generally show lowered thresholds for pain and perceptions related to low intensity stimulation, such as urgency, distension or bloating (eg, Song et al). While these results do not enable us to draw conclusions about the underlying sensory mechanisms, they argue against a selective sensitisation of specialised nociceptive pathways. The theoretical implications may go further, as the clinical findings make a case for intensity coding, meaning the aggregate input rather than nociceptor activation alone contribute to the complex symptoms of IBS. Thus, peripheral and/or central sensitisation may alter the perception of low and high threshold sensory input from the gastrointestinal tract. This model also explains patient experiences of lasting pain, which cannot be related to ongoing luminal distensions at pressures exceeding 50 mm Hg, symptom exacerbations triggered by physiological phenomena, such as increases in wall tension, or symptomatic improvement by defaecation or after administration of spasmolytics. Closing the loop back to animal experiments, enhanced visceromotor responses at low distending pressures after transient colitis also suggest a less selective sensitisation of sensory pathways. The new data presented in this issue of Gut strengthen the argument that there are specialised nociceptive pathways in the gastrointestinal tract. The results are convincing and support a role for such nociceptors in acute pain (ie, during high intensity stimulation). Sensitisation of specific nociceptive pathways may also contribute to post-infectious IBS and similar functional disorders. Yet, nociceptor activation alone may not be sufficient or even necessary to cause the chronic pain or discomfort our patients describe.