B.L. Flashcards
Descending control can be facilitatory as well as inhibitory. In what ways is descending control dynamic?
Changing balance between degree of inhibition + degree of facilitation on pain processing in spinal cord
Dynamic in..
Emotional states: (fear - inhibition tends to predominate)
Pathological states: central control systems change in fever / sickness response (heightened transmission of nociceptive information)
Development: neonate facilitation predominates (neonatal exquisitely sensitive to nociceptive input and can have major impact on future pain experiences)
Descending facilitation now known to contribute to phenomenon of central sensitisation
What did Rexe provide?
Rexe’s Laminar Organisation of the Spinal Cord (1970s)
On cytoarchitectonic grounds (shape/organisation of neurons in spinal cord grey matter): delineated a number of concentrically organised laminae
* Dorsal horn = laminae I-V * Ventral horn = laminae VI-X
Although described purely on anatomical grounds, neurons in different laminae also serve different functions
What did Rexe provide?
Rexe’s Laminar Organisation of the Spinal Cord (1970s)
On cytoarchitectonic grounds (shape/organisation of neurons in spinal cord grey matter): delineated a number of concentrically organised laminae
* Dorsal horn = laminae I-V * Ventral horn = laminae VI-X
Although described purely on anatomical grounds, neurons in different laminae also serve different functions
(lamination described by Rex may have functional relevance based on where different fibre types terminate in spinal dorsal horn)
What are thermoreceptors mainly innervated by?
Free nerve endings that are predominantly αδ and C
Nociceptors come in different ‘types’ - what are they based on
Type of stimulus required to activate them (e.g. high threshold mechanoreceptors, thermal nociceptors, polymodal)
Most polymodal respond to heat, high threshold mechanical + chemical activation
- Deep receptors: less well studied than cutaneous receptors (invasive procedures can affect what you are trying to study)
- Viscera: can cut/burn without feeling, but distention of gut will be felt - finding adequate stimulus to activate nociceptors is difficult
What are examples of morphological studies?
DEGENERATION: observed after sectioning dorsal roots or portions of them - central projections degenerate but with a different delay related to diameter of fibre (Aβ, Aδ or C)
(monitoring time course of degeneration means can deduce where different fibre types terminate in cord
AXONAL TRANSPORTS: cut peripheral nerves into dye/markers, transported into spinal cord
AUTORADIOGRAPHY: of spinal cord sections following injections of radioactive amino acids into dorsal root
- Lots of overlap between what these different fibres are connected to in the periphery
What is a technique for functional identification + anatomical organisation of primary afferent terminals in the dorsal horn?
Record from individual DRG cell in preparation with intact peripheral axon (so can test what it responds to: touch/pinch/heat/chemical etc)
*Recording from nerve must be intracellular
- Then inject with a dye after killing animal - allow transport of substance into the dorsal horn → histological sectioning to map where the terminations are of individual neurons that have been characterised physiologically
- Very technically challenging! But useful, functional information
What did Cervero 1996 review article show about skin mechanical input?
Info from diff experiments; input from skin/muscle/viscera and where the fibres ended in spinal cord grey matter
Skin mechanical input: αβ mainly in neck of dorsal horn (lamina III,IV&V), C low threshold fibre in lamina II (superficial dorsal horn)
What did Cervero 1996 review article show about skin mechanical input?
Info from diff experiments; input from skin/muscle/viscera and where the fibres ended in spinal cord grey matter
Skin mechanical input: αβ mainly in neck of dorsal horn (lamina III,IV&V), C low threshold fibre in lamina II (superficial dorsal horn)
What did Cervero 1996 review article show about skin nociceptors?
Skin nociceptors: αδ + C fibres mainly in lamina I + II
* some aδ in lamina V but very little C fibre input
What did Cervero 1996 review article show about skin nociceptors?
Lamination first described by Rex may have functional relevance based on where different fibre types terminate in spinal dorsal horn
What did Cervero 1996 review article show about skin nociceptors?
αβ (large diameter) down into lamina IV (4 - where most proprioceptive/tactile input goes)
αδ fibres activated neurons in lamina I (and some in lamina V - deep dorsal horn)
C fibres predominantly lamina II
*Different neurons in dorsal horn have long processes (Neurons in lamina V can make contact with lamina I/II), therefore Termination in the lamina does not mean that neurons within those laminae are exclusively activated by that fibre type
How are dorsal horn neurons classified?
1970s: defined dorsal horn neurons based on their responses to cutaneous inputs (Class 1, 2 and 3)
1 = lam 3+4 2 = lam 5 3 = lam I
What are class 1 DH neurons?
Low threshold / mechanoreceptive
Only respond to LOW INTENSITY stimulation in periphery (mainly αβ, rapidly conducting myelinated):
Mainly in III (3) + IV (4)
= (but some in V/VI)
What are class 2 DH neurons?
WDR / polymodal / mutlireceptive / convergent / lam V
Respond to both HIGH intensity and LOW intensity stimuli e.g. heat, acid.
Predominantly lamina V. (input is αβ + aδ + MAYBE C). *important - does class 2 fibre have C fibre input?
What are class 3 DH neurons?
High threshold / nociceptive specific (NS)
Only respond to HIGH intensity (40 degree heat, pinch, chemicals, algesic chemicals), input almost exclusively αδ + C fibres (in different combinations).
Predominantly in lamina I (superficial, surface)
Know less about lamina I (surface) because its easier to record from lamina V. (deep) Surface of cord = pulsatile movement with circulatory system/respiration - recording from small neuron difficult. Deep in DH more stable and easier to make long lasting recordings (hours).
Workman & Lumb (1990). What did they show about class 2 DH neurons?
Lamina V recording - intact animals anaesthetised
After killing animal, inject dye through electrode
Histological sections - examine exactly where recording was from
L6 recording (input from hind paw) - stimulus-time histogram, number of APs per second
Cell responses to prod, brush, PINCH (main) and noxious heat. Firing rate for noxious heat same as brush, therefore - the way these neurons signal nociceptive input still great debate, as can’t just be frequency of firing if noxious heat has same rate as brush
Debate: which cells are important in pain pathways?
Class 3 in lamina I that only respond to nociceptive input, or class 2 in lamina V with low and high intensity input?
Lumb (1990). What shown about viscerosomatic neurons?
They are convergent, in the sense that they have input from the skin and the viscera
No private visceral pain pathways from gut to brain
- shares its pathways with somatic input (efficient)
- not very economical use of nervous system to have private pathway as not often aware of gut/heart etc.
Particular cell recorded from responds to splanchnic nerve (visceral) but also receptive field on flank (skin)
* basis of referred pain = brain learns that activity from this cell is from the skin * injury/pathology in gut, nociceptive afferents activated (visceral afferents) but brain interprets of skin
How can class 2 DH neurons be classified?
C +ve or C -ve
Functional significance of classification
Class 2 activated by low + high intensity stimuli, but response to high intensity stimulation could be mediated by αδ, C, or both.
Most are C-positive (90%)
Important subset are not activated by C fibres (C-negative) - no matter how high intensity the stimulus, can never evoke a C fibre response
How can you identify C positive vs C negative
Anaesthetised rat, recording from DH neuron in lamina V, electrical stimulus in receptive field on skin
Responds with APs at very short latency (because α fibres conduct more rapidly, get into spinal cord more quickly) - response to α fibres, probably low threshold
After delay (about 200ms) - get burst of APs that are conveyed by C fibres (because conducting much more slowly - less than 1m/second
Lab work: descending control of neurons with and without C fibre input - important differences in the way they are regulated by the brain
* both behavioural and clinical significance
What did Cervero 1996 review article show about fibre tract OUTPUT from DH neurons?
PSDC = post-synaptic dorsal column pathway
SCT = spinal-cervical tract
STT = spino-thalamic tract (note: many ascending pain pathways that are not SST)
SRT = spino-reticular tract
SMT = spino-mesencephalic tract
SCbT= spino-cerebellar tract
AM - autonomic motor system, SM - somatic motor system
What did Cervero 1996 review article show about DH OUTPUT to the STT?
STT: some cells of origin in lamina I + V, but also some in lamina VI (6)
*Often assumed that DH all sensory + ventral horn all motor (many cells of origin of the STT are in lamina VII(7), VIII(8) (ventral horn) and X(10) (around central canal)
What did Cervero 1996 review article show about DH tract OUTPUT to the SRT?
SRT: largely nociceptive, taking info to reticular formation in brainstem
cells of origin - lamina I, V, VII, VIII, X (STT without 6)
Often is collaterals of STT (tracts share common parts of pathways then send of branches and innervate different parts of neuroaxis)
What did Cervero 1996 review article show about DH tract OUTPUT to the PSDC?
Used to be considered purely low threshold (as the dorsal columns are)
* dorsal columns: input through dorsal root, axons don’t enter grey matter → straight to dorsal column nuclei * but there are collaterals at the lower spinal cord that do synapse within the cord - the neurons they synapse with form the post-synaptic dorsal column pathway (synapse between primary afferent and dorsal column nuclei) * now know this also subserves nociceptive function
- Cerebellum neglected in pain research although it lights up in MRI scans!!
- SCbT: just one way of getting to cerebellum, has cells of origin in lamina I+V, (also IV, VI, VII, VIII)
What did Cervero 1996 review article show about DH tract OUTPUT to the PSDC?
Used to be considered purely low threshold (as the dorsal columns are) - from 3/4/5
Dorsal columns: input through dorsal root, axons don’t enter grey matter → straight to dorsal column nuclei
But collaterals at the lower spinal cord do synapse within the cord - the neurons they synapse with form the post-synaptic dorsal column pathway (synapse between primary afferent and dorsal column nuclei)
* now know this also subserves nociceptive function
What did Cervero 1996 review article show about DH tract OUTPUT to the cerebellum?
SCbT: just one way of getting to cerebellum, has cells of origin in lamina 1+5, (also IV, VI, VII, VIII)
Cerebellum neglected in pain research although it lights up in MRI scans!!
Sensory discriminative pain?
Perception / detection
Intensity, location, duration
Somatosensory cortex
Specific thalamic nuclei: VPL, VPM, VMPo
Components of: STT, SCT, PSDC
