Pain is an essential
learning mechanism which is important for survival and avoiding damage.
Effects of 5-HT on pain perception did not found to be confounded
by mood changes.
Pain is an essential learning mechanism which is important for survival and avoiding damage. Pain processing is linked to various regions of brain that integrates information to form a pain matrix. It occurs due to combination of multiple factors such as stimulus intensity, emotional and contextual state and individual past experiences which contributes to the expectation of pain. There is a high prevalence of chronic pain and limited treatment as compared to acute pain. The preliminary treatment against chronic pain is selective serotonin re uptake inhibitors (SSRIs) that acts by increasing the level of serotonin (5-HT) in the brain. The use of serotonin inhibitors generates mixed results, but their mechanism of action on pain processing is not known. The specific role of 5-HT in the modulation of pain processing is shown by certain animal studies. Descending inhibitory serotonergic spinal-raphe projections arises from raphe magnus of nucleus and an endogenous descending pain-modulating network is formed. The pain-modulating network is capable of mediating both the facilitation and inhibition of nociceptive processing. On the other hand, ascending serotonergic pain pathways projects from midbrain dorsal-raphe nucleus to limbic and adjacent forebrain sites and controls the attentional processing of nociception. There is a correlation between chronic pain and maladaptive neuroplastic changes leading to pain sensitivity. It was evident from previous studies that 5-HT levels within the brain can cause abnormal neuroplastic changes associated with chronic pain; however, the role of 5-HT as a modulator in pain perception remains uncertain. The analgesic properties of 5-HT-modulating antidepressants are responsible for role of 5-HT in the pathophysiology of several human chronic pain disorders. There is an uncertainty in apparent analgesic effects of 5-HT-modulating drugs as a direct consequence of increased availability of 5-HT or as a secondary effect of mood changes. A technique called an acute TRP depletion (ATD) that employs the global depletion of its precursor tryptophan (TRP), has been used to determine the role of 5-HT in humans. There was an improvement in pain tolerance and mood with supplementation of TRP in healthy individuals, but still there is a debate on the involvement of mood changes induced by the ATD.
Rationale behind the research:
There exists a debate concerning the role of 5-HTs in pain perception, so this study was conducted to determine the pain perception associated with use of 5-HTs and examining its effects of ATD on heat pain threshold and tolerance, attentional manipulation of nociceptive processing and mood in human volunteers
Objective:
To investigate the utility of ATD in determine the role of 5-HT in pain perception with an attempt to dissociate the effects from mood changes
Study outcome measure:
Time points: Baseline, 4 hours and 6 hours
Study Outcomes
The results
of this study established a connection between the reduction of global 5-HT via ATD and an alteration of pain
perception with altered mood state. A clear role of 5-HT in pain perception was
demonatrated by ATD which significantly reduced both threshold and tolerance of
the thermode temperature. Also, ATD significantly affects cognitive appraisal
of the sensory-discriminatory aspects of pain, but it did not significantly
affect distraction-induced analgesia. The study also supports the paradigm that
low levels of 5-HT correlate to pain sensitisation. It is helpful in
understanding possible mechanisms of chronic pain states and variable
effectiveness seen in the use of SSRIs for chronic pain.
The study establishes a role of 5-HT in the cognitive and noncognitive aspects of pain processing and chronic pain. However, and future studies will be integral to improve individual treatment choice for patients with chronic pain.
Psychopharmacology (2017) 234:2929–2939
5-HT modulation of pain perception in humans
Sarah L Martin et al.
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