Biology of Pain

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Biology of Pain Bruce Lynn Lecture 1, PHOL
G008, Fundamentals of Pain
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• 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)

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• Nature of threatening stimuli?
• Commonest - Mechanical overstressing from
  external or internal source. Note, need FAST
  system to respond, rapid protective reflexes.
• Heat. More than half land surface of the earth
  will exceed 45 for at least one month in the
  year.
• 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.

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• Nature of threatening stimuli?
• Commonest - Mechanical overstressing from
  external or internal source. Note, need FAST
  system to respond, rapid protective reflexes.
• Heat. More than half land surface of the earth
  will exceed 45 for at least one month in the
  year.
• 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.

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• In many animals, 2 major sub-classes of
  nociceptor, matching 2 broad requirements
• Mechanical nociceptors.
• 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.

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Play worm moviehttp//www.bio.unc.edu/faculty/go
ldstein/lab/crawl.mov
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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)
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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.
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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.
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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!
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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.