Chapter 18-7. Nociceptors
Recommended post: 【Biology】 Chapter 18. Sensory system
1. Overview
3. Step 1. Sensory discrimination
4. Step 2. Ascending pain pathway
5. Step 3. Pain pathway in the brain
6. Step 4. Endogenous analgesic system
1. Overview
⑴ Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage experience (Source: International Association for the Study of Pain (1979))
① Nociception (noxious stimulus, nociception): A warning sensation for tissue damage
② Pain (pain): A subjective feeling learned through nociception
⑵ Nociceptors
① Nociceptor (noxious receptor, nociceptor): A receptor that responds only to noxious stimuli; response increases as the intensity of noxious stimulus increases
② Heat and cold are also sensed by nociceptors
⑶ Dimensions of pain
① Sensory-discriminative dimension (sensory discriminative)
○ Intraneural microelectrode technique (intraneural microelectrode technic)
Figure 1. Intraneural microelectrode technique]
② Cognitive-evaluative dimension (cognitive-evaluative)
③ Affective-motivational dimension (affective-motivational)
⑷ Subjective pain intensity rating (PRI)
① labour pain, clinical pain syndrome, pain after accident
② Burning pain (complex pain syndrome, causalgia)
Figure 2. Subjective pain intensity rating
2. Nociceptor receptors
Also called TRP(transient receptor potential channel).
■ Humans, ■ fish, ■ flies, ■ worms
⑴ TRPA: TRPA1, TRPA1
① TRPA1: Cold nociception, noxious chemicals · mustard oil (mustard oil), etc.
⑵ TRPC: TRP, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7
⑶ TRPM: GON-2, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8
① TRPM8: Cold nociception, menthol (Menthol), etc.
⑷ TRPML: CUP-5, TRPML1, TRPML2, TRPML3
⑸ TRPN: NOMPC, NOMPC, NOMPC
⑹ TRPP: TRPP2, TRPP3, TRPP5, PKD-2, PKD-2
⑺ TRPV: OSM, NAN, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6
① TRPV1: Heat nociception, chili pepper · capsaicin (Capsaicin), etc.
3. Step 1. Sensory discrimination
⑴ Receptive pain: Nociceptors generate warning signals for external stimuli
Figure 3. Shapes and characteristics of major nociceptors
① Aα and Aβ fibers
○ Large diameter and myelinated: Good nerve-signal conduction → sensitive
○ Proprioception, light touch
○ Proprioception: Perceiving the body’s position
○ Pain can be inhibited via proprioception; forgetting pain by exercising hard; evolutionarily reasonable
○ Heat threshold: None
○ Aβ fibers: lamina Ⅲ, lamina Ⅳ
② Aδ fibers: Sharp nociception accompanied by tissue damage
○ Medium diameter and myelinated: Nerve-signal conduction is moderately good → initial pain
○ Mechanical, thermal, chemical nociception. Involved in initial pain
○ Heat threshold: ~53 ℃ (type Ⅰ), ~43 ℃ (type Ⅱ)
○ lamina Ⅰ, deeper layers
③ C-polymodal fibers (C-polymodal nociceptor): Related to pain memory; by recruiting emotion to remember pain, enables practical responses to pain later pain later
○ Small diameter and unmyelinated: Poor nerve-signal conduction → delayed pain
○ Non-nociceptive sensation for temperature and itch
○ Mechanical, thermal, chemical nociception. Involved in delayed pain
○ Heat threshold: ~43 ℃
○ lamina Ⅱ
④ Silent fibers (silent nociceptor)
Figure 4. Silent fibers
⑵ Inflammatory pain (inflammatory pain): Surveillance of microenvironmental changes around an injury
① 1st. Lesion occurs
② 2nd. Due to the lesion, bradykinin, 5-HT, prostaglandin, H+, histamine stimulate dorsal root ganglion neurons
○ Bradykinin: A potential vasodilator
○ The English term for 척추신경절 뉴런 is dorsal root ganglion neuron
③ 3rd. Stimulated dorsal root ganglion neurons secrete CGRP and substance P to induce vasodilation
④ 4th. At the same time, dorsal root ganglion neurons secrete CGRP and substance P to stimulate mast cells (mast cell)
○ Not only mast cells, but also macrophages, neutrophil granulocytes, etc. are involved
⑤ 5th. Mast cells secrete histamine and NGF to stimulate dorsal root ganglion neurons (positive feedback)
⑥ 6th. If the stimulus applied to dorsal root ganglion neurons exceeds the threshold, the signal is transmitted to the spinal cord (spinal cord)
⑶ Neuropathic pain (neuropathic pain)
① A pathological condition due to damage to neural pathways
② Examples: Carpal Tunnel syndrome, spinal cord injury, thalamic stroke
⑷ Dorsal root ganglion (DRG; dorsal root ganglion)
① A swelling on the dorsal-root side where the ventral and dorsal roots of the spinal nerve join
② The cell bodies of nociceptive nerves are in the DRG
○ Likewise, the cell bodies of other sensory nerves are also in the DRG
○ Cell bodies of nociceptive nerves: Account for 75% of the DRG, small and dark cells
○ Central processes form synapses in the superficial layers of the dorsal horn
○ Nociceptive nerves: Action potential duration ↑, shows a hump
③ Classification of cells by threshold
○ High threshold cell: Aδ, C fibers, 30~40% of STT
○ Wide dynamic range (WDR) cell: Aδ, Aβ fibers; indirectly receives C-fiber input; 50~60% of STT
○ Low threshold cell: Aβ fibers, 5~10% of STT
④ Neurotransmitters: Glutamate (glutamate), substance P (substance P), CGRP, etc.
⑤ Gate control theory (gate control theory): A theory that pain transmitted to the brain can be regulated or altered via interactions between pain-transmission cells and fibers in the spinal cord in the spinal cord
○ There is a system that can weight affective value to recognize importance for touch or pain
○ Theory of Melzack and Wall, Nobel Prize theory
Figure 5. Gate control theory model
4. Step 2. Ascending pain pathway
① Ascending tract 1. Pain, temperature sensation, light touch: Decussation occurs at the corresponding spinal ganglion
② Ascending tract 2. Proprioception, touch: Decussation occurs at the medullary pyramidal tract
③ Descending tract. Regardless of sensory modality, decussation occurs at the medullary pyramidal tract
Figure 6. Decussation of nociception
⑵ Spinoreticular tract
⑶ Spinomesencephalic tract
⑷ Spinohypothalamic tract
⑸ Polysynaptic dorsal column pathway
⑹ Effects of multiple pathways
① Improved sensory discrimination
② Arousal response (arousal response)
③ Affective-motivational response (affection-motivational response)
④ Autonomic response (autonomic response)
⑤ Spinal reflex (spinal reflex)
⑥ Improved endogenous analgesic system
5. Step 3. Pain pathway in the brain
⑴ 3rd - 1st. Thalamus, ACC, amygdala → PAG
⑵ 3rd - 2nd. PAG → RVM
① PAG (periaqueductal gray): Located around the central aqueduct of the midbrain, involved in descending modulation of pain
② Pain is the most fundamental sensation for human survival, so it remains in the oldest gray-matter structures of the brain
○ Processing the importance of pain (e.g., gate control theory) involves evolutionarily very old PAG and limbic cortex (Limbic Cortex)
⑶ 3rd - 3rd. RVM → dorsal horn
6. Step 4. Endogenous analgesic system
⑴ Definition: An analgesic system in the central nervous system (Basbaum & Fields, 1978)
⑵ Type 1. Stimulation-produced analgesia (stimuation-produced analgesia)
① Analgesia induced by electrical stimulation of PAG in rats (Reynolds, 1969)
② Analgesia induced by stimulating midline brain structures (PAG, PVG, NRM) as well as cerebellum, thalamus, hypothalamus, internal capsule, caudate nucleus, etc.
⑶ Type 2. Endogenous opioid system
① Receptor proteins for opioids (opioid) exist in the CNS
○ Opioids (opiate-like agents, opioid): A type of chemical substance similar to morphine (morphine)
○ Enkephalin (enkephalin): An endogenous peptide that binds to opioids to produce analgesic effects
② Mainly matches SPA sites near the CNS midline
7. Abnormal pain phenomena
⑴ Double pain: Essentially a normal phenomenon
① Initial pain (initial pain): Aδ nociceptors; sharp and well-demarcated
② Delayed pain (delayed pain): C-polymodal nociceptors; poorly demarcated
⑵ Chronic pain (chronic pain)
① Definition: Arbitrary, but pain that lasts 3~6 months or longer
② Characteristics: Involved in learning and memory processes; mostly a symptom of neuropathy; depends on psychosocial state
⑶ Referred pain (referred pain)
① A symptom in which pain due to actual visceral tissue damage is felt at another site such as the skin
○ Example: Instead of sensing that the aorta hurts, it is perceived as a stiff back (a matter of frequency)
② Convergence-projection theory (convergence-projection theory): Because visceral organs and dermatomes converge to the same point on the spinal cord, pain is felt in the dermatome connected to the corresponding organ organ
⑷ Hyperalgesia (hyperalgesia): Exaggerated perception of minor pain
① Primary hyperalgesia: Injury site; mechanical and thermal hyperalgesia; peripheral sensitization
② Secondary hyperalgesia: Surrounding area; mechanical hyperalgesia; central sensitization
③ Mechanism: Axons of Aβ receptors form synapses with two or more neurons, amplifying the signal to more than double
④ Example: Erythromelalgia (erythromelalgia)
⑸ Allodynia (allodynia): Feeling pain even from stimuli that would not normally cause pain
⑹ Phantom limb (phantom limb pain, phantom limb): Feeling pain in a body part that has been amputated and is no longer present
⑺ Congenital analgesia (congenital analgesia)
Input: 2018.12.01 00:01
Revised: 2026.01.20 20:30