Mol Pain
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Recent data suggest that corneal somatosensory dysfunction may be the underlying cause of severe dry eye symptoms in the absence of ocular surface pathology seen in a subset of patients diagnosed with “dry eye syndrome.” This subset of patients tends to demonstrate a unique constellation of symptoms that are persistent, more severe, and generally respond poorly to current dry eye therapies targeting inadequate or dysfunctional tears. A growing body of literature suggests that symptoms in these patients may be better characterized as neuropathic ocular pain rather than dry eye. In these patients, dry eye symptoms are often associated with numerous comorbid pain conditions and evidence of central pain processing abnormalities, where eye pain is just one of multiple overlapping peripheral manifestations. In this review, we discuss the concept and potential mechanisms of chronic overlapping pain conditions as well as evidence for considering neuropathic ocular pain as one of these overlapping pain conditions.
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The spinal dorsal horn receives input from primary afferent axons, which terminate in a modality-specific fashion in different laminae. The incoming somatosensory information is processed through complex synaptic circuits involving excitatory and inhibitory interneurons, before being transmitted to the brain via projection neurons for conscious perception. ⋯ However, at present, we have only a limited understanding of the neuronal circuitry within this region, and this is largely because of the difficulty in defining functional populations among the excitatory and inhibitory interneurons. The recent discovery of specific neurochemically defined interneuron populations, together with the development of molecular genetic techniques for altering neuronal function in vivo, are resulting in a dramatic improvement in our understanding of somatosensory processing at the spinal level.
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It is documented that sensory transmission, including pain, is subject to endogenous inhibitory and facilitatory modulation at the dorsal horn of the spinal cord. Descending facilitation has received a lot of attention, due to its potentially important roles in chronic pain. ⋯ It also provides the neuronal basis to link emotional disorders such as anxiety, depression, and loss of hope to somatosensory pain and sufferings. In this review, I will review a brief history of the discovery of brainstem-spinal descending facilitation and explore new information and hypothesis for descending facilitation in chronic pain.
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Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. ⋯ Monoclonal antibodies for chronic pain have the potential to overcome the limitations of current treatment options, but strategies to ensure their appropriate use need to be determined.
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Primary sensory neurons are responsible for transmitting sensory information from the peripheral to the central nervous system. Their responses to incoming stimulation become greatly enhanced and prolonged following inflammation, giving rise to exaggerated nociceptive responses and chronic pain. The inflammatory mediator, prostaglandin E2 (PGE2), released from the inflamed tissue surrounding the terminals of sensory neurons contributes to the abnormal pain responses. ⋯ Under normal conditions, cAMP activates primarily protein kinase A. After inflammation, cAMP also activates the exchange proteins activated by cAMP (Epacs) to produce exaggerated PGE2-mediated hyperalgesia. The role of cAMP-Epac signaling in the generation of hypersensitivity is the topic of this review.