Nearly every advance in modern medicine, from diagnosis to treatment, has benefited from animal studies. Basic research has made vital contributions to all aspects of medical care, including our understanding of pain pathophysiology.
However, the applicability of these findings to humans remains limited. “Translation from animal to human is hindered by many obstacles, in particular with the subject of pain, where the human organism and mind interact in quite a unique way,” Claudia Sommer, MD, a professor of neurology at the University of Würzburg in Germany, told Clinical Pain Advisor.
Even so, valuable insights have been gained by the direct study of humans with chronic pain. In a special issue on pain, Science published a review article by Dr Sommer that highlights some of the most notable developments, including the 3 below.1
Quantitative sensory testing (QST)
QST is a “psychophysical method that uses a battery of sensory stimuli with predetermined physical properties following specific protocols,” and it is “able to capture and quantify stimulus-evoked negative and positive sensory phenomena,” Dr Sommer wrote.
These sensory phenomena should indicate the type of nerve fiber involved because of the unique characteristics of the fibers. The use of QST has led to the unexpected discovery that small nerve fibers are involved in Parkinson’s disease, fibromyalgia, and other disorders in which large nerve fibers were believed to be the only type involved.2,3 These findings suggest that pain in such disorders may be in part due to primary or secondary peripheral nociceptors.
In other disorders, QST has led to the identification of “sensory profiles” that may reflect the pain pathophysiology of individual patients and facilitate targeted treatment planning medicine.
For example, one study found that patients in whom QST revealed preserved nociceptor function were more responsive to the antiepileptic drug oxcarbazepine than patients with impaired nociceptor function.4
In other research, the 8% capsaicin patch appeared to be more effective in patients whose QST results indicated hyperalgesia vs small-nerve fiber loss.5
Further research will be required to determine the utility of QST sensory phenotyping in individualized treatment. Such data may be most informative when combined with neurophysiological and molecular phenotyping.
Genetic Testing (PAIN IS IN THE GENES)
Though human genomic studies have not yet yielded substantial gains in this area of medicine, research focusing on monogenic disorders have led to highly valuable discoveries.
“One successful example is the monogenic pain diseases based on mutations in voltage-gated sodium channels (Nav),” said Dr Sommer. “Here, the sodium channel blocking anti-epileptics, which are usually second- to third-line in the treatment of neuropathic pain, have been proven to be useful analgesics.”
Investigations in this area have established a role for voltage-gated sodium channel activity in pain etiology and elucidated the nature of its malfunction in various genetic mutations.
For example, erythromelalgia and paroxysmal extreme pain disorder can result from gain-of-function mutations of Nav1.7 ion channels, while congenital analgesia is caused by a loss-of-function mutation in Nav1.7. In addition, mutations of the genes for Nav1.7, Nav1.8, and Nav1.9 have been found in as many as 30% of patients with idiopathic small-fiber neuropathy (SFN).6
Other studies have linked a single-nucleotide polymorphism in the SCN9A gene [rs6746030, substitution of arginine-1150 with tryptophan (R1150W)] with pain in disorders such as Parkinson’s disease and interstitial cystitis, and it may render affected individuals more sensitive to pain.
“With the exception of rare monogenetic diseases like the ones mentioned above, changes in one gene or its product often do not have a major effect on pain perception,” Dr Sommer noted in the review.
11/14/2016
Continue reading the full article from Psychiatry Advisor