Neuroscience
-
An accumulating body of evidence suggests that the hypothalamic neuropeptide oxytocin (OT) has a modulatory effect on pain processing. Particularly strong evidence comes from animal models. Here, we review recent advances in animal research on the analgesic effects of OT and discuss possible target sites of OT within descending and ascending pain pathways in the brain. ⋯ Moreover, we also address how OT might alleviate pain by influencing socio-emotional components in humans. We conclude that further investigating specific OT and OT-sensitive circuits, which modulate pain processing especially in primates, will improve our understanding of OT-analgesic effects. In human research, the increased use of neuroimaging and autonomic measures might help to bridge the gap to animal studies.
-
In the understanding of chronic pain, hypotheses derived from psychological theories, together with insights from physiological assessments and brain imaging, highlight the importance of mechanistically driven approaches. Physical system changes, for example following injury, can result in alterations of psychological processes and are accompanied by changes in corticolimbic circuits, which have been shown to be essential in emotional learning and memory, as well as reward processing and related behavior. In the present review, we thus highlight the importance of motivational, reward/pain relief, and fear learning processes in the context of chronic pain and discuss the potential of a mechanistic understanding of chronic pain within a clinical perspective, for example for the development of therapeutic strategies. We argue that changes in these mechanisms are not only characteristic for chronic pain, reflecting consequences of the disorder, but are also critically involved in the transition from acute to chronic pain states.
-
Comparative Study
Human vs. Mouse Nociceptors - Similarities and Differences.
The somatosensory system allows us to detect a diverse range of physical and chemical stimuli including noxious ones, which can initiate protective reflexes to prevent tissue damage. However, the sensation of pain can - under pathological circumstances - outlive its usefulness and perpetrate ongoing suffering. Rodent model systems have been tremendously useful to help understand basic mechanisms of pain perception. ⋯ Additionally, co-expression of Ret and TrkA was also found to be more abundant in human neurons. Moreover, the neurofilament heavy polypeptide was detected in all human sensory DRG neurons compared to a more selective expression pattern observed in rodents. To our knowledge, this is the first time that such detailed comparative analysis has been performed and we believe that our findings will direct future experimentation geared to understand the difficulties we face in translating findings from rodent models to humans.
-
Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI). ⋯ The results suggest that injury-induced amygdaloid oxidative stress that drives TRPA1 promotes neuropathic pain behavior. This pronociceptive effect involves suppression of medullospinal serotonergic feedback-inhibition acting on the spinal 5-HT1A receptor. While the CeA is involved in mediating the nerve injury-induced pronociception, it may not be a critical relay for the recruitment of medullospinal feedback-inhibition.
-
Cortical reorganization has been proposed as a major factor involved in phantom pain with prior nociceptive input to the deafferented region and input from the non-deafferented cortex creating neuronal activity that is perceived as phantom pain. There is substantial evidence that these processes play a role in neuropathic pain, although causal evidence is lacking. Recently it has been suggested that a maintenance of the cortical representation of the former hand area is related to phantom pain. ⋯ Although often introduced as contradictory, we suggest that cortical reorganization, preserved limb function and peripheral factors interact to create the various painful and nonpainful aspects of the phantom limb experience. In addition, the type of task (sensory versus motor), the interaction of injury- and use-dependent plasticity, the type of data analysis, contextual factors such as the body representation and psychological variables determine the outcome and need to be considered in models of phantom limb pain. Longitudinal studies are needed to determine the formation of the phantom pain experience.