A topical review 1 of the literature on congenital pain insensitivity highlights the complexity of pain perception as it relates to anatomical and physiological defects—congenital, or acquired—and concludes the deficits may preferentially affect carious components of the medial pain system, including the anterior cingulate cortex. Because the studies reviewed failed to locate the origin of the deficits observed, the authors of this review emphasize the need for careful assessment of all pain sensory components in patients to better understand the pathways involved in pain perception. They also propose that gene mapping afflicted patients may help provide understanding about the molecular mechanisms at work in pain perception. This could lead to more effective and selective therapies in the future.
What’s at Stake?
There is overwhelming evidence about the necessity of pain perception to human survival. Studies of patients with congenital disorders that inhibit their abilities to experience or respond to pain show that many people afflicted with pain insensitivity die during childhood due to their inability to notice discomfort from illness or injuries. A recent lack of scholarly interest in the United States about pain insensitivity necessitated an updated review of the clinical literature of the phenomenon to help better understand its mechanisms and origins. The authors of the review stress the importance of a better and more complete assessment of the components of pain perception and insensitivity—possibly through gene mapping of patients—in order to provide more comprehensive and effective therapeutic measures in the future.
About Pain Insensitivity
Medical literature about pain insensitivity has existed since the 1930’s. The condition—in which patients are either unable to experience, have a reduced sensitivity to, or can feel, but have little-to-no-reaction to pain, has been termed “congenital general pure analgesia,” “congenital universal indifference to pain,” and “congenital absence of pain” over the years. More recently, the predominate terms used to describe the affliction have been “congenital insensitivity to pain” or “congenital indifference to pain.” The terms, which have been used interchangeably, have now been distinguished to reference two separate groups of patients, depending upon the specific origins and symptoms of their condition.
Insensitivity to Pain
Patients who are insensitive to pain have a reduced or inability to experience pain sensations. They may be unable to distinguish between different types, intensities, or qualities of painful stimuli.
Indifference to Pain
Patients with a congenital indifference to pain can feel pain but have no affective response to it. They will not react to painful stimuli by withdrawing from the source of pain.
In the past, individuals with pain insensitivity were diagnosed and treated based upon a set of observational criteria that included unaccounted for wounds or lesions and excluded from the diagnosis when their pain impairment that could have been caused by other underlying conditions or injuries. As technological medical diagnostic advancements allowed for better assessment methods of nerve pathologies, patients with irregular sensory nerves who in the past might have been classified as “congenital indifference to pain,” are now classified under a subheading of “congenital pain insensitivity arising from peripheral neuropathies of various types”.
Components of Pain Perception
There are three recognized components to pain perception—sensory-discriminative, affective-motivational, and cognitive-evaluative. Those suffering from pain insensitivity may demonstrate their sensorial deficits across a broad range of responses to stimuli.
Pain Discrimination Loss
When a patient loses the ability to discriminate between types of painful or uncomfortable stimuli, they may not be able to distinguish between sharp and dull sensations or hot and cold temperatures. They may, however, experience a negative emotional reaction to these stimuli, even though they cannot name the source of their discomfort.
Affective-Motivational Response Deficit
Patients with affective-motivational response loss experience painful and uncomfortable stimuli but have no reaction to it. When a patient has this condition, also known as “Pain Indifference,” they do not withdraw from painful stimuli. This makes them vulnerable to burns and other injuries. Some patients with affective-motivational deficits may have a negative reaction to pain but will not withdraw from it and will allow repeated painful stimulus to be applied without objection.
Pathways to Pain
Pain perception is modulated in large part by two ascending pathways—the lateral pain system projecting through lateral thalamic nuclei to the somatosensory cortex, and the medial pain system, which projects to the anterior cingulate cortex and insula through the medial thalamic nuclei. The sensory-discriminative pain component is modulated by the lateral system, and the affective response to pain is modulated through the medial system.
Pain perception impairments may be caused by lesions in specific regions of the brain or loss of peripheral afferents, which may create deficits in sensory and affective pain responses. Depending on the size and location of a lesion, the impairment may be localized and subtle or severe.
Congenital and Hereditary Pain Insensitivity Syndromes
Many children with peripheral neuropathies experience sensory-discriminative and affective-motivational impairments and may be diagnosed with hereditary sensory and autonomic abnormalities (HSAN). There are five sub-categories of HSAN currently recognized, and all of the types are known to exhibit small-diameter C and A-delta fiber involvement. These fibers are responsible for the transmission of pain sensation.
There is a wide spectrum of HSAN features, including an inability to experience the sensation of burns, digit mutilation, and injuries to the joints. Many of the patients are unable to distinguish between the type and intensity of painful stimuli and do not take precautionary measures to prevent the recurrence of pain or remove themselves from painful situations. Genetic causes have been investigated, and specific genes have been identified for many forms of HSAN, but the condition is at present uncurable.
Congenital Pain Indifference
Patients with congenital indifference to pain may have normal sensory reactions when examined but experience painless injuries as early as infancy. On past examination of peripheral nerve samples, clinicians found no abnormalities and thus characterized the disorder as a deficit in pain response. Because no analysis of nerve fiber density was performed on these patients, it is unclear if their disorder might have been caused by a selective loss of nerve fibers.
It has been suggested that these patients might have been experiencing a neurotransmitter disturbance that affected their central sensory processing pathways. Other reports indicate that this type of disorder may have peripheral and central nerve origins.
Deficits in pain perception can also occur as a result of brain lesions in areas that modulate the processing of painful stimuli. This can create congenital pain insensitivity-type disorders. When these lesions occur in the anterior cingulate cortex or insular cortex, they may affect the function of the medial pain system and cause a loss of affective-motivational function. Sensory-discriminative components of pain may be affected by lesions in the primary and secondary somatosensory cortex affecting the lateral pain system.
Patients with affective-motivational deficits who retain a sense of sensory discrimination are suffering from ‘asymbolia for pain.’ They may experience pain but have no—or an unusual—response to it, such as laughter. It is possible an impairment of the sensory-discriminative pain components, without affective-motivational components, could be caused by central lesions.
The variations of pain insensitivity syndromes and the deficits they cause make clear the complexity of pain perception physiological and anatomical processes. Though it remains unclear exactly how the disorder originates, current research suggests the need for a more complete assessment of how the different components of pain perception affect sensory intensity and response in HSAN patients. Genetic mapping may assist clinicians in developing better, more selective therapies for patients in the future.