Endorphins, Hormones, and Neuropeptides

Endorphins, Hormones, and Neuropeptides
one rapidly activated psychoneuroendocrine mechanism

through which a placebo stimulus may reduce both depression

and pain is produced by stimulating the endorphin system. 16

Research on endorphins is a relatively new area of study in the
field of psychoneuroimmunology. Original research by Levine
et al 96 suggested that the pain relief noted in placebo studies could
be explained by the simple mechanism of endorphin-mediated ac-
tions. The original emphasis on endorphins and enkephalins was
plausible, considering their known modulation of pain and mood
functions. This position was further supported by later observa-
tions that depression increased chronic clinical pain 156 and that
decreased activity in endogenous opioids may be part of the path-
ophysiology of depression. 157 With the information that placebo
can stimulate endorphins, Levine et al 96 believed that an explana-
tion for the action of placebos had finally been found. Further-
more, research showed that a endorphin-mediated, pain-
suppressant placebo effect could be abolished with the use of
Nalaxone, an opiod antagonist. 158 The same authors went on to
further show that endorphin-mediated placebo effects penetrated
other physiologic systems besides pain management. 159 However,
this hypothesis failed to account for the broad spectrum of pla-
cebo effects as well as for the fact that the analgesia associated with
hypnosis was not affected by an opioid antagonist. 160,161 It is
important to note that later literature suggested that Levine et al 96
were not entirely wrong in implicating the role of endorphins in
the placebo mechanism; rather, these researchers were right for the
wrong reason.

Endorphins are mainly derived from three precursor proteins
(by separate biochemical processes). 162 These opioid peptides are

TABLE 6-2 Effects of Endorphins on the Immune System

IMMUNE SYSTEM FUNCTION

ENDORPHIN EFFECTS)

Lymphocyte production

Increased and decreased

Chemotaxis

Increased

T-cell sensitivity to prostaglandin E 2

Increased

Antibody production

Increased and decreased

Complement

Binding of fractions C5B-C9

T-cell proliferation

Modulation of

Natural killer cell function

Modulation of

B-cell differentiation

Modulation of

released from central and peripheral areas in response to pain,
stress, and emotions and perform many physiologic functions, of
which analgesia is but one. 163 However, it is becoming evident
that the boundaries between the CNS and the immune system are
not as clear as once thought. The several known effects of endor-
phins on immune system function are listed in Table 6-2. 164

When the functions of neurotransmitters such as endorphins
are found to have such an intimate relationship with immune
integrity, the paradigm of a body with functions performed inde-
pendently by its parts β€” a Newtonian type of thinking β€” begins to
lose credibility. To further blur the already hazy distinction
between the CNS and the immune system, research demon-
strated that endorphins and peptide hormones, such as adreno-
corticotropic hormone, thyroid-stimulating hormone, human
chorionic gonadotropin, and luteinizing hormone, are produced
by lymphocytes. 164

It is clear that the demarcation between the CNS and the
immune system is impossible to distinguish. The brain and the
immune system are the only tissues in the body that have a
memory, and the level of communication between the two argues
a taxonomy that identifies them as one. Evidence of the innerva-
tion of the thymus gland, bone marrow, spleen, and lymph nodes
supports the finding that the immune system is subject to efferent
CNS information. 164 In addition, studies demonstrating the
atrophy of the thymus and lymphatic tissues in the absence of
growth hormone, 165 adrenocorticotropic hormone, and increased
steroid production by adrenal cells after interferon stimulation,
indicate that β€œin the future it will be difficult to distinguish the
receptors and signals that are used within and between the neuro-
endocrine and immune system.” 164

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