Pain
-
Patients with radicular low back pain (radicular LBP, sciatica) frequently describe their pain as "shooting" or "radiating." The dictionary meaning of these words implies rapid movement, and indeed, many sufferers report feeling pain moving rapidly from the lower back or buttock into the leg. But, others do not. Moreover, the sensation of movement is paradoxical; it is neither predicted nor accounted for by current ideas about the pathophysiology of radicular LBP. ⋯ The velocity of movement or expansion was also variable. By cross-referencing sensations experienced in the sciatica and trigeminal neuralgia cohorts with known signal processing modes in the somatosensory system, we propose testable hypotheses concerning the pathophysiology of the various vectorial sensations reported, their direction and velocity, and the structures in which they are generated. Systematic evaluation of qualitative features of "shooting" and "radiating" pain at the time of diagnosis can shed light on the pain mechanism in the individual patient and perhaps contribute to a better therapeutic outcomes.
-
Patients with chronic pain often report being sensitive to pain at night before falling asleep, a time when the synchronization of cortical activity is initiated. However, how cortical activity relates to pain sensitivity is still unclear. Because sleep is characterized by enhanced cortical delta power, we hypothesized that enhanced cortical delta power may be an indicator of intensified pain. ⋯ Chemogenetic activation of GABAergic neurons in ACC enhanced EEG delta power and lowered mechanical pain thresholds simultaneously in naive mice. However, chemogenetic inhibition of ACC GABAergic neurons could not block mechanical allodynia. These results provided compelling evidence that elevated EEG delta power is accompanied with aggravated neuropathic pain, whereas decreased delta power attenuated it, suggesting that enhanced delta power can be a specific marker of rising chronic neuropathic pain and that wake-promoting compounds could be used as analgesics in the clinic.
-
Chronic pain and anxiety symptoms are frequently encountered clinically, but the neural circuit mechanisms underlying the comorbid anxiety symptoms in pain (CASP) in context of chronic pain remain unclear. Using viral neuronal tracing in mice, we identified a previously unknown pathway whereby glutamatergic neurons from layer 5 of the hindlimb primary somatosensory cortex (S1) (Glu), a well-known brain region involved in pain processing, project to GABAergic neurons in the caudal dorsolateral striatum (GABA). ⋯ In addition, the optical activation of Glu terminals in the cDLS produced anxiety-like behaviors in naive mice. Overall, the current study demonstrates the putative importance of a novel Glu→GABA pathway in controlling at least some aspects of CASP.
-
Observational Study
Sub-optimal learning of tactile-spatial predictions in patients with complex regional pain syndrome.
In complex regional pain syndrome (CRPS), tactile sensory deficits have motivated the therapeutic use of sensory discrimination training. However, the hierarchical organisation of the brain is such that low-level sensory processing can be dynamically influenced by higher-level knowledge, eg, knowledge learnt from statistical regularities in the environment. It is unknown whether the learning of such statistical regularities is impaired in CRPS. ⋯ This caused greater precision on prediction errors, resulting in predictions that were driven more by momentary spatial changes and less by the history of spatial changes. These results suggest inefficiencies in higher-order statistical learning in CRPS. This may have implications for therapies based on sensory retraining whose effects may be more short-lived if success depends on higher-order learning.
-
Localizing pain is crucial because it allows for detecting which part of the body is being hurt and identifying in its surrounding which stimulus is producing the damage. Nociceptive inputs should therefore be mapped according to somatotopic ("which limb is stimulated?") and spatiotopic representations ("where is the stimulated limb?"). Because the body posture constantly changes, the brain has to realign the different spatial representations, for instance when the arms are crossed with the left hand in the right space and vice versa, to adequately guide actions towards the threatening object. ⋯ Relative to the uncrossed posture, sighted participants' performances were decreased when the hands were crossed, whatever the instruction be. Early blind participants' performances were affected by crossing the hands during spatial instruction, but not during anatomical instruction. These results indicate that nociceptive stimuli are automatically coded according to both somatotopic and spatiotopic representations, but the integration of the different spatial reference frames depends on early visual experience and ongoing cognitive goals, illustrating the plasticity and the flexibility of the nociceptive system.