Ganong's Review of Medical Physiology, 23rd Edition

178
SECTION III
Central & Peripheral Neurophysiology

Despite intensive study, relatively little is known about the
brain mechanisms that cause tolerance and dependence.
However, the two can be separated. Absence of
β
-arrestin-2
blocks tolerance but has no effect on dependence.
β
-Arrestin-
2 is a member of a family of proteins that inhibit heterotrim-
eric G proteins by phosphorylating them.
Acupuncture at a location distant from the site of a pain
may act by releasing endorphins. Acupuncture at the site of
the pain appears to act primarily in the same way as touching
or shaking (gate-control mechanism). A component of stress-

induced analgesia appears to be mediated by endogenous opi-

oids, because in experimental animals some forms of stress-

induced analgesia are prevented by naloxone, a morphine

antagonist. However, other forms are unaffected, and so other

components are also involved.

ACETYLCHOLINE

Epibatidine, a cholinergic agonist first isolated from the skin

of a frog, is a potent nonopioid analgesic agent, and even more

FIGURE 11–5
Local-circuit interneurons in the superficial dorsal horn of the spinal cord integrate descending and afferent
pathways. A)
Possible interactions of nociceptive afferent fibers, interneurons, and descending fibers in the dorsal horn. Nociceptive fibers termi-
nate on second-order spinothalamic projection neurons. Enkephalin (ENK)-containing interneurons exert both presynaptic and postsynaptic in-
hibitory actions. Serotonergic and noradrenergic neurons in the brain stem activate opioid interneurons and suppress the activity spinothalamic
projection neurons.
B
1
)
Activation of nociceptors releases glutamate and neuropeptides from sensory terminals, depolarizing and activating pro-
jection neurons.
B
2
)
Opiates decrease Ca
2+
influx leading to a decrease in the duration of nociceptor action potentials and a decreased release of
transmitter. Also, opiates hyperpolarize the membrane of dorsal horn neurons by activating K

• conductance and decrease the amplitude of the
  EPSP produced by stimulation of nociceptors.
  (From Kandel ER, Schwartz JH, Jessell TM [editors]:
  Principles of Neural Science,
  4th ed. McGraw-Hill, 2000.)

Nociceptor

Nociceptor

Projection

neuron

Morphine

Morphine

Glutamate

Neuropeptides

Control

No input

No input + opiates

Sensory input Sensory input + opiates

Opiate

Neuropeptides

Ca2+

Glutamate

ENK

Projection

neuron

Norepinephrine

Serotonin

B 1 Sensory input

A

B 2 Sensory input + opiates/opioids

Control

Control

Enkephalin

Enkephalin

Control

Ca2+

Enkephalin Enkephalin