|M.Sc Student||Nahman Averbuch Hadas|
|Subject||Pain Processing and its Relation to Autonomic Function in|
Chemotherapy Induced Polyneuropathy Patients
|Department||Department of Medicine||Supervisors||Professor David Yarnitsky|
|Dr. Dorit Pud|
|Full Thesis text - in Hebrew|
Common side effect of several chemotherapy agents is polyneuropathy, which is often painful. The reason why some patients who acquire neuropathy due to neuro-toxic chemotherapy develop painful neuropathy while others do not is not known. During recent years pain inhibition effect had been shown for the afferent vagal activity. Since chemotherapy may affect the vagus as part of the polyneuropathy, and causes decrease in its inhibitory effect, we propose that the extent of vagal damage may explain the difference in pain intensity among different patients
Our aim was to examine the relationships between the extent of vagal damage and clinical and experimental pain.
This cross sectional studied 27 patients and 30 healthy women. Among patients, 12 suffered from painful neuropathy (painfulNP) while 15 suffered from nonpainful neuropathy (nonpainfulNP).
Subjects were tested for sensory thresholds (cold, warm, mechanical), heat pain thresholds, mechanical temporal summation (TS) and 'diffuse noxious inhibitory control' (DNIC) effect. For autonomic assessment, HRV was recorded during baseline, pain and post pain. The heart beats ratios of deep breathing test and Valsalva manoeuvre were calculated.
PainfulNP patients showed significantly higher warm sensation thresholds (p=0.026), higher TS (p=0.02) and less efficient DNIC (p=0.05), in comparison to nonpainfulNP patients. Correlations were found between spontaneous pain level and cold sensation thresholds in the foot and forearm (r=-0.4; p=0.043, r=-0.54; p=0.007, respectively), TS (r=0.52; p=0.005), and DNIC (r=-0.40; p=0.05). DNIC and TS were also inter-correlated (r=0.56; P=0.004). Regarding the autonomic function; higher parasympathetic function was associated with lower pain scores (r= 0.56; p=0.0083), higher adaptation (r= -0.495, p=0.022) to tonic heat pain stimulation and more efficient DNIC (r=0.47; p=0.03). However, no correlations were found between autonomic function and spontaneous pain.
Among controls, higher parasympathetic function was associated with lower pain scores (r= -0.485, p=0.007) and higher adaptation (r= -0.578, p=0.0008) of tonic heat pain stimulation.
PainfulNP patients had higher loss of sensation which reflects more severe neuropathy and, in line, an enhanced pain modulation with higher TS and less efficient DNIC. We suggest that pain modulation is more pronociceptive among painfulNP patients. Pathophysiologically it is either a priori pronociceptive system that facilitates the neuropathy into being painful, or a priori normal pain modulation system is enhanced in the presence of pain.
In addition, inverse relationship between parasympathetic function and experimental pain were found among patients and healthy groups. These relationships are probably emanated from the neuro-anatomical connections between autonomic and pain-processing brain centers.