Updates & Features

Prof. Aziz’s Presentation

Prof. Aziz began his presentation by introducing the idea that pain perception is multidimensional, with sensory-discriminative, affective-motivational and cognitive-evaluative aspects all impacting on pain perception. Affective-motivational and cognitive-evaluative factors vary considerably from person to person, modulating how much pain is enhanced centrally. If a person is considered a neurotic character/phenotype, they may perceive their pain as greater compared to an extroverted characteristic/phenotype.^1,2

Prof. Aziz presented data contributing to the identification of distinct pain ‘clusters’: neurotic or extroverted phenotypes. The following factors were presented:

• Personality traits³
• The pattern of autonomic nervous system (ANS) responses to pain³
• Hypothalamic-pituitary-adrenal axis responses³
• Polymorphisms of the serotonin transporter (5-HTTLPR)^3,4
• Central nervous system responses⁵

Discussion Points

The first discussion point was relating to data on the ANS’s role in modulating pain hypersensitivity using the acid-induced oesophageal sensitisation model. In this model, central sensitisation (centrally-mediated reduction in pain tolerance) was achieved by an acid infusion (injury) to the lower oesophagus and was demonstrated by sensitisation in the upper oesophagus. Using this model, it was shown that subjects that had received the acidic injury (central sensitisation) had a significantly greater reduction in cardiac vagal tone (CVT), compared with those who had not received an injury (not centrally sensitised). Therefore, patients who had lower CVT had greater oesophageal pain sensitisation to acid. These findings led to the question: if you artificially increase the CVT, will this reduce/prevent central oesophageal pain hypersensitivity? To analyse this, the paradigm of slow deep breathing to increase CVT was used. It was shown that when slow deep breathing was performed, there was a drastic improvement in pain tolerance post-acid infusion, suggesting that the ANS has a role in pain hypersensitivity.⁶ Indeed, Prof. Aziz’s response went on to say that slow deep breathing, along with transcutaneous vagal nerve stimulation have shown efficacy in pain conditions, and he anticipates that there will be considerable further research on this fascinating therapeutic area of parasympathetic nervous system (PNS) modulation.

The next question focused on the link between the neurotic phenotype and acid-induced oesophageal sensitisation. Prof. Aziz mentioned that his team are currently working on a clinical study in patients with gastroesophageal reflux disease. This study hypothesises that the patients with a greater reduction in parasympathetic tone will sensitise more and have a reduced pain threshold.

The role and interaction of pharmacotherapy in/with PNS modulation was then enquired about. Prof. Aziz informed us that there have not been many pharmacotherapeutic studies into this field, however, there have been pharmacotherapeutic studies using clonidine that have demonstrated efficacy in pain management.

One of the final discussion points was regarding the physiological pathways of the antinociceptive effects of transcutaneous vagal nerve stimulation. One pathway responsible is the brainstem-mediated descending pathways to the cervical spinal cord inhibiting pain perception. A second pathway via a descending pain inhibitory loop, activated at the brain level due to the second order PNS neurons activating the limbic system was described by Prof. Aziz. It is known that the descending pain modulatory pathways originate in the limbic cortex, which merge with peripheral nerves, suggesting that there can be pain modulation centrally as well.