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					          Biology of Pain

              Bruce Lynn

Lecture 1, PHOL G008, Fundamentals of Pain
Biology of Pain

Key role: PROTECTION
•From external threats – sensors
(nociceptors) in the skin
•From internal overstresses, e.g. to the
joints
•Of injured tissues, by minimising use,
through increased pain sensitivity
(hyperalgesia)
Nature of threatening stimuli?
1. Commonest - Mechanical overstressing – from
   external or internal source. Note, need FAST system
   to respond, rapid protective reflexes.
2. Heat. More than half land surface of the earth will
   exceed 45° for at least one month in the year.
3. Irritant chemicals
•   "True" irritants, external to organism, e.g. capsaicin
•   Agents generated in association with inflammation,
    e.g. bradykinin.
Note, no sensing of UV or of ionising radiation.
Nature of threatening stimuli?
1. Commonest - Mechanical overstressing – from
   external or internal source. Note, need FAST system
   to respond, rapid protective reflexes.
2. Heat. More than half land surface of the earth will
   exceed 45° for at least one month in the year.
3. Irritant chemicals
•   "True" irritants, external to organism, e.g. capsaicin
•   Agents generated in association with inflammation,
    e.g. bradykinin.
Note, no sensing of UV or of ionising radiation.
In many animals, 2 major sub-classes of
   nociceptor, matching 2 broad
   requirements:
1. Mechanical nociceptors.
2. Polymodal nociceptors (sensitive to all 3
   stimuli: mech, heat, irritants).
Most mammalian tissues have both types,
  including skin, muscles, joints, hollow visceral
  organs.
Find same pattern even in very simple animals,
   e.g. Parasitic nematode, C. elegans.
               Play worm movie

http://www.bio.unc.edu/faculty/goldstein/lab/crawl.mov
Sensory cells in C. elegans.
The ASH, FLP and OLQ neurones sense touch to the nose. The ASH
cells in addition sense noxious chemicals and so have a polymodal
response profile.
AVM and ALM neurones sense light touch to the anterior region
whereas PLM neurones sense light touch to the posterior region.
PVD neurones sense only intense mechanical stimuli, i.e. they have a
mechanical nociceptor profile.
The anatomical abbreviations are L, left, R, right, D, dorsal, V, ventral.
The figure shows the left lateral side of the worm.
                      From (Kaplan & Horvitz, 1993)
Relation of nociceptor activity to pain.
NOT SIMPLE!
ITCH. Some cutaneous stimuli, e.g. histamine,
activate nociceptors but cause itch. Not
understood why some nociceptor activity
causes itch, some pain. Same afferents
involved in both.
Nociception without pain. Some tissues
have nociceptors, but no pain. Notably smaller
bronchioles in lung, plenty nociceptors, trigger
protective (cough) reflexes, but no pain.
Relation of nociceptor activity to
pain. NOT SIMPLE! (continued)
Pain without injury. Note IASP definition of
pain:
An unpleasant sensory and emotional
experience associated with actual or potential
tissues damage, or described in terms of
tissue damage.
Last phrase relates to situations where pain is
reported when no injury or inflammation is
present. For example, phantom limb pain;
pain in certain neuropathic disorders.
Clinical viewpoint on pain
Famous surgeon LeRiche wrote in 1930s:
“Defence reaction? Fortunate warning? But as a matter of
fact, the majority of diseases, even the most serious,
attack us without warning. When pain develops….it is too
late…. The pain has only made more distressing and
more sad a situation already long lost. In fact, pain is
always a baleful gift, which reduces the subject of it, and
makes him more ill than he would be without it.”
LeRiche is thinking of chronic pain conditions associated with cancer,
or with difficult-to-treat neuropathic diseases. In fact, there are many
useful clinical pain situations, e.g. Pain from twisted ankle, stops
further use and possible further damage; Angina, makes one rest and
so reduces load on heart. In addition, many pain patterns are very
helpful in diagnosis.
But must agree with him about toothache!
Pain, good or bad?
Would it be better to have all tissues
like the lungs? Possibly, as long as
protective reflexes were effective.
Where pain and protective reflexes are
absent, leads to problems. For
example, congenital insensitivity to
pain, rare, but has high morbidity, often
associated with serious joint damage
due to overstress.

				
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