20.11:
Nociception
Nociception, generally referred to as pain, is the process through which a noxious stimulus is transmitted through the peripheral and central nervous systems to warn off potential harm or injury.
When a damaging signal is detected, nociceptors, free nerve endings, are activated. Nearby mast cells release chemicals, such as histamines, while macrophages secrete cytokines, small proteins that are critical factors in immune signaling.
Simultaneously, the axons of the nociceptors transmit the signal to the dorsal horn of the spinal cord, mainly via two different pain fibers.
The first ones to be activated are the thinly myelinated A-delta fibers, which conduct immediate sharp and well-localized pain at a very fast speed, to allow the body to withdraw from the harmful stimulus.
The other type of axons are C fibers, which conduct slowly as they are unmyelinated and transmit prolonged burning pain.
From the spinal cord the pain signals cross over and travel to the brain stem, followed by the thalamus and somatosensory cortex where the pain signals are interpreted to determine the location of injury.
Additional brain regions process the pain, notably corticolimbic structures, including the amygdala and prefrontal cortex that relate to emotional memories and cognition. Ultimately, the multiple interactions within the brain contribute to the subjective perception that individuals experience.
20.11:
Nociception
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the organism avoid noxious stimuli.
The immune system plays an essential role in pain pathology. Upon encountering noxious stimuli, immune cells such as mast cells and macrophages present at the site of injury release inflammatory chemicals such as cytokines, chemokines, histamines, and prostaglandins. These chemicals attract other immune cells such as monocytes and T cells to the injury site. They also stimulate nociceptors, resulting in hyperalgesia—a more intense response to a previously painful stimulus, or allodynia—a painful response to a normally innocuous stimulus such as light touch. Such pain sensitization helps protect the injured site during healing.
In some cases, pain outlives its role as an acute warning system if sensitization fails to resolve over time. Chronic pain—persistent or recurrent pain lasting longer than three months—often accompanies inflammatory conditions such as rheumatoid arthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen reduce pain by inhibiting the synthesis of the inflammatory molecules prostaglandins. However, NSAIDs and opioids currently used to combat pain suffer from severe side effects and the potential for addiction. Therefore, understanding the mechanisms underlying pain pathology can help develop more effective drugs to suppress pain perception with less severe negative side effects.
Suggested Reading
St. John Smith, Ewan. “Advances in Understanding Nociception and Neuropathic Pain.” Journal of Neurology 265, no. 2 (2018): 231–38. [Source]
Pinho-Ribeiro, Felipe A., Waldiceu A. Verri, and Isaac M. Chiu. “Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation.” Trends in Immunology 38, no. 1 (January 2017): 5–19. [Source]