Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 11

Somatosensory Pathways 179

potent synthetic congeners of this compound have been devel-
oped. Their effects are blocked by cholinergic blocking drugs,
and as yet there is no evidence that they are addictive. Con-
versely, the analgesic effect of nicotine is reduced in mice lack-
ing the
α
4
and
β
2
nicotine cholinergic receptor subunits.
These observations make it clear that a nicotinic cholinergic
mechanism is involved in the regulation of pain, although its
exact role remains to be determined.

CANNABINOIDS

The cannabinoids anandamide and palmitoylethanolamide

(PEA) are produced endogenously and bind to CB

1

and CB

2

receptors, respectively. Anandamide has been shown to have

an analgesic effect, and there are anandamide-containing neu-

rons in the periaqueductal gray and other areas concerned

with pain. When PEA is administered, it acts peripherally to

augment the analgesic effects of anandamide.

CHAPTER SUMMARY

■

Discriminitive touch, proprioception, and vibratory sensations

are relayed via the dorsal column (medial lemniscus) pathway to

SI. Pain and temperature sensations are mediated via the ven-

trolateralspinothalmic tract to SI.

■

The ascending pathways mediating sensation are organized so-

matotopically all the way from the spinal cord to SI.

■

Descending pathways from the mesencephalic periaqueductal

gray inhibit transmission in nociceptive pathways. This de-

scending pathway includes a synapse in the ventromedial me-

dulla (raphé nucleus) and the release of endogenous opiates.

■

Morphine is an effective antinociceptive agent that binds to en-

dogenous opiate receptors in the midbrain, brain stem, and spi-

nal cord.

■

Anandamide is an endogenous cannabinoid that binds to CB

1

receptors and acts centrally as an analgesic agent.

MULTIPLE-CHOICE QUESTIONS

For all questions, select the single best answer unless otherwise directed.

1. A ventrolateral cordotomy is performed that produces relief of
   pain in the right leg. It is effective because it interrupts the
   A) left dorsal column.
   B) left ventral spinothalamic tract.
   C) right lateral spinothalamic tract.
   D) left lateral spinothalamic tract.
   E) right corticospinal tract.


2. Which of the following does
   not
   exert an analgesic effect?
   A) morphine
   B) cholinergic antagonists
   C) adrenergic antagonists
   D) substance P antagonists
   E) anandamide


3. A 40-year-old man loses his right hand in a farm accident. Four
   years later, he has episodes of severe pain in the missing hand
   (phantom limb pain). A detailed PET scan study of his cerebral
   cortex might be expected to show
   A) expansion of the right hand area in his right somatic sensory
   area I (SI).
   B) expansion of the right-hand area in his left SI.
   C) a metabolically inactive spot where his hand area in his left
   SI would normally be.
   D) projection of fibers from neighboring sensory areas into the
   right-hand area of his right SI.
   E) projection of fibers from neighboring sensory areas into the
   right-hand area of his left SI.

CLINICAL BOX 11–3

Motivation & Addiction

Forebrain neurons in the

ventral tegmental area

and

nu-

cleus acumbens

are thought to be involved in motivated

behaviors such as reward, laughter, pleasure, addiction, and

fear. These areas have been referred to as the brain’s

reward

center

or

pleasure center. Addiction,

defined as the re-

peated compulsive use of a substance despite negative

health consequences, can be produced by a variety of differ-

ent drugs. According to the World Health Organization, over

76 million people worldwide suffer from alcohol abuse, and

over 15 million suffer from drug abuse. Not surprisingly, alco-

hol and drug addiction are associated with the reward sys-

tem. The

mesocortical dopaminergic neurons

that project

from the midbrain to the

nucleus accumbens

and the fron-

tal cortex are also involved. The best studied addictive drugs

are opiates such as morphine and heroin, cocaine, ampheta-

mine, ethyl alcohol, cannabinoids from marijuana, and nico-

tine. These drugs affect the brain in different ways, but all

have in common the fact that they increase the amount of

dopamine available to act on

D

3

receptors

in the nucleus ac-

cumbens. Thus, acutely they stimulate the reward system of

the brain. On the other hand, long-term addiction involves

the development of

tolerance,

that is, the need for increas-

ing amounts of a drug to produce a high. In addition, with-

drawal produces psychologic and physical symptoms. Injec-

tions of

β

-noradrenergic antagonists or

α

2

-noradrenergic

agonists in the bed nucleus of the stria terminalis reduce the

symptoms of opioid

withdrawal,

and so do bilateral lesions

of the lateral tegmental noradrenergic fibers. One of the

characteristics of addiction is the tendency of addicts to re-

lapse after treatment. For opiate addicts, for example, the re-

lapse rate in the first year is about 80%. Relapse often occurs

on exposure to sights, sounds, and situations that were previ-

ously associated with drug use. An interesting observation

that may be relevant in this regard is that as little as a single

dose of an addictive drug facilitates release of excitatory neu-

rotransmitters in brain areas concerned with memory. The

medial frontal cortex, the hippocampus, and the amygdala

are concerned with memory, and they all project via excita-

tory glutamatergic pathways to the nucleus accumbens.