Pain- general

Property C-fibre A(delta)-fibre A(beta) fibre Neuronal size Small- 0.4±1.2 mm Medium- 2±6 mm Large->10 mm Conduction velocity Slow- unmyelinated - 2 m/s Fast- myelinated- 20 m/s[C1]  Fast- myelinated- 30±100 m/sec Adaption rate       Threshold for activation High High High Termination in spinal cord laminae Laminae I & II, and then projects to V (polysynaptic) Laminae I & V (monosynaptic) Laminae I & II & V >> not very well studied Sensation Poorly localised[C2] - Burning pain Well localised[C3] - Sharp pain Sharp pain modality thermal, mechanical, and chemical stimuli- polymodal dangerously intense mechanical or to mechanothermal stimuli   Receptive field Relatively large-  presumably because the detection of pain is more important than its precise localization Relatively large- clusters of sensitive spots            [C1]That a proportion of A-fibre nociceptive neurones have fibres that conduct in the Aa/b range has been confirmed  with intracellular recordings in DRG neurones in vivo in several species.  [C2]effective in causing reflex changes such as cardiovascular or respiratory changes  [C3]important property of an exteroceptive pathway, enabling precise and rapid withdrawal responses from a specific localised noxious stimulus

Property C-fibre (nociceptive)                     C-fibre (mechanoreceptor) Stimulus High intensity mechanical stimuli low intensity mechanical stimuli moving very slowly across the skin Neurotransmitter release SP, CGRP Low levels of CGRP         A-Fibre (nociceptive) A-fibre (non-nociceptive) Action potentials longer somatic AP and AHP durations than A-fibre LTM neurones   The AP overshoot is greater than that for LTM units   Conduction velocity Slower conduction velocity           Ad-fibre nociceptive Aa/b-nociceptive[C1]  Thresholds High thresholds Lower thresholds              [C1]Why is it important to distinguish between Ad- and Aa/bfibre nociceptive neurones? One reason is the need to distinguish between the contributions of Aa/b-fibre LTM units and Aa/b-fibre nociceptive units to the development of hypersensitivity (hyperalgesia and allodynia) after peripheral nerve injury.

  Stimulus type DRG neurons Molecule Mechanical Chemical Thermal (degrees celcius) Size (S/M/L) Afferent type TRPV1   Low pH, capsaicin >42 S C TRPV2     >52 SML A TRPV4/3 Noxious- mech/ stretch   >32 SM NF-rich A TRPM8[C1]    Methanol <22 S C-cooling TRPA1[C2] / ANK TM1 Nox mech   <17 S C-cold (visceral) ASIC / ASIC1   Low pH     C DRASIC / ASIC3 Mech? Low pH Heat     P2X3 Mech? ATP   S Noxious              [C1]Responsive to changes in temp >> not noxious cold receptor  [C2]Some controversy- is it noxious cold or not?? See evidence

Adequate Stimulus Receptor Adaptn Afferent Innn CUTANEOUS RECEPTORS Mechanoreceptors mechanical Meissner Pacinian Hair Cells Ruffini Merkel RA RA RA RA SA Aβ Aβ Aβ Aβ Aβ Thermoreceptors (LT) heat & Cool Free endings variable Aδ & C Nociceptors: HTMs Thermal Polymodal   mechanical heat or Cold chem/heat/mech   Free endings Free endings Free endings   SA/RA slow slow   Aδ most Aδ & C C, few Aδ DEEP RECEPTORS Muscle: spindles       nociceptors mechanical polymodal/mech Spindle Free endings SA/RA SA/RA Ia, Ib, II Aδ & C Viscera: pressure       nociceptors mechanical polymodal/mech Free endings SA/RA Aβ Aδ & C

CLASS DESCRIPTION AFF INPUT LAMINA 1 Low Threshold Mechanoreceptive Aβ III, IV V,VI 2 Wide Dynamic Range Polymodal Multireceptive Convergent Lam V Type[C1]  Aβ, Aδ & C Aβ & Aδ I IV, V, X VII, VIII 3[C2]  High Threshold Nociceptive Specific (NS) Nocireceptive Aδ Aδ & C C I V,X, VII, VIII  [C1]Different names  [C2]Class 2 and 3 are involved in nociception

C vs A-fibres

nociceptive vs non-nocicpetive

TRP receptors

cutenous and deep receptors summary

classification of Dorsal horn neurons