A Review of the Emotional Aspects of Neuropathic Pain: From Comorbidity to Co-Pathogenesis
Pain Ther
A Review of the Emotional Aspects of Neuropathic Pain: From Comorbidity to Co-Pathogenesis
0 R. Torta V. Ieraci (&) F. Zizzi Department of Neuroscience ''Rita Levi Montalcini'', University of Turin , Turin , Italy
Neuropathic pain is characterized by both sensory and affective disturbances, supporting the notion that pain and mood disorders share common pathogenetic mechanisms. Moreover, biological and neuroimaging data show that common brain areas are involved in the modulation of painful and emotional experiences. Improved understanding of the molecular mechanisms underlying the role of neuroinflammation in regulation of affective behavior in neuropathic pain states is important for the development of novel therapeutic strategies. Psychological issues must be considered a factor influencing treatment and outcome in patients with neuropathic pain. Funding: Pfizer, Italy.
Mood disorders; Molecular mechanisms; Neuroinflammation; Neuropathic pain; Therapeutic strategies
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Neuropathic pain is associated with a
substantial economic burden for both individuals and
society [1]. There is strong evidence available to
suggest that patients with neuropathic pain
experience worse health-related quality of life
(QOL) than the general population [2–4], and a
negative effect of neuropathic pain has also
been reported in other health conditions [5, 6].
Chronic pain with a neuropathic component
has been shown to be associated with worse
QOL, greater psychological distress, increased
interference with sleep, and loss of more
workdays than chronic pain without a neuropathic
component [
7
].
Neuropathic pain is characterized by sensory
symptoms such as gain or loss of somatosensory
function, burning and evoked pain, as well as
abnormal temporal summation [8]. Nerve
injury models have shown sensory disturbances
to arise from interactions between neurons,
immune and immune-like glial cells, and other
immune cell-derived inflammatory mediators,
including cytokines and chemokines, ATP,
histamine, bradykinin and prostaglandins; in this
sense, neuropathic pain is a neuro-immune
disorder [9]. This report discusses the
relationships between mood disorders and neuropathic
pain, with a focus on the pathogenetic
mechanisms linking these two disorders, and reviews
available treatment strategies.
Compliance with Ethics Guidelines
This article is based on previously conducted
studies and does not involve any new studies of
human or animal subjects performed by any of
the authors.
MOOD DISORDERS IN PATIENTS
WITH NEUROPATHIC PAIN
Clinically, neuropathic pain is characterized by
both sensory and affective disturbances, and
this frequent comorbidity supports the notion
that pain and mood disorders share some
common pathogenetic mechanisms [
10
]. It is
important, therefore, to treat an affective
disorder that coexists with pain. The affective
disturbances associated with pain include working
memory dysfunction, impaired cognition,
decreased appetite, depression, anhedonia,
disruptions to sleep cycles, and impaired familial
and social interactions [
11
]. The most common
regions of the brain involved with pain in
affective disturbances are the nucleus
accumbens, the medial prefrontal cortex and the
periaqueductal gray [
12
]. However, while
available research highlights that there are some
psychological variables common across
different disorders, every pathology is characterized
by some specific psychological aspects [
10
].
Neurological disorders associated with
neuropathic pain are characterized by important
associations between psychosocial factors and
pain intensity.
The importance of emotional aspects of pain
is particularly evident for depression and
anxiety [
10
]. Depression is predictive for pain in
many conditions, including chronic
musculoskeletal pain, multiple sclerosis, post-stroke
pain and Parkinson’s disease [
13–16
]. Moreover,
the presence of a neuropathic component
correlates with higher values for depression and
anxiety [
17–19
]. Depression can also be
associated with alexithymia, with evidence suggesting
that if these two factors are present together,
they have a combined influence on the affective
component of pain [20]. Anxiety is frequently
present in patients with chronic pain
conditions, and appears to be correlated with pain
intensity [
17, 21
]. Neuropathic pain is
associated with specific psychological factors: fear
linked to the painful sensation and perceived
danger associated with different activities may
cause irritability and social withdrawal [10].
Importantly, an inadequate response of
neuropathic pain to various drug therapies constitutes
a substantial unmet need [1].
PATHOGENETIC MECHANISMS
OF PAIN AND AFFECTIVE
DISTURBANCES
Supraspinal neuroinflammation has a potential
role in the development of affective disorders in
patients with neuropathic pain conditions.
Evidence suggests sickness behavior, cognitive
impairment, depression and other
neuropsychiatric disor (...truncated)