Pain in chronic pancreatitis: a salutogenic mechanism or a maladaptive brain response?

Abstract

Pain in chronic pancreatitis is frequently refractory to medical and even surgical treatment. This refractoriness leads us to believe that a pancreas-independent, brain-mediated mechanism must be responsible. If so, several scenarios are worth considering. First, chronic pain could be the consequence of undesirable neuroplastic changes, by which pathology becomes established and causes disability. Alternatively, pain may be linked to the salutogenic (from salutogenesis, the Latin word for health and well-being) central nervous system response (we defined 'salutogenic response' as the specific modulation of the immune system induced by brain activity changes) to promote healing of the injured viscera. If so, chronic pain could index the ongoing nervous system attempt to promote healing. In this review, we discuss (1) the mechanisms of pain in chronic pancreatitis; (2) potential brain-related salutogenic mechanisms, and (3) the potential relationship of these two factors to the disease status. Furthermore, we consider these aspects in light of a new approach to treat visceral pain: transcranial magnetic stimulation, a noninvasive method of brain stimulation.

Fig. 1.

In this figure, we show that pancreatic inflammation stimulates local nociceptors in the pancreas that convey this information to subcortical nuclei, such as thalamic nuclei, resulting in the activation of a neural cortical network that involves pain-related structures responsible for behavior changes (which may result in a beneficial response as pain forces the individual to rest for recovery, for instance), but may also stimulate potential ‘salutogenic response structures‘, which might increase or decrease pancreatic inflammation, thus generating a maladaptive or beneficial response, respectively.

Fig. 2.

Nervous system activity changes that follow pancreatic inflammation. These changes occur in all levels of the nervous system: from the peripheral nerves to central nervous structures such as spinal cord, subcortical and cortical structures. Activity changes in these areas are responsible for sustaining chronic pain.

Fig. 3.

Factors that contribute to the experience of chronic pain and the interrelation between these factors and pain. For instance, psychological factors alter cortical activity and vice versa and both factors can modulate pain severity. Furthermore, severity of visceral inflammation is associated with the severity of immune response that in turn modulates cortical activity that in response might modulate back inflammation severity, ultimately, resulting in a regulation of pain severity.