Pregabalin as a Co-Adjuvant with Tramadol in Management of Neuropathic Pain in Pediatric Cancer

Background: Painful neuropathies are common among pediatric patients with cancer and may arise from different cancer treatment modalities. The role of adjuvants in the treatment of cancer pain has been well recognized for many years and they have become the cornerstone for the treatment of neuropathic pain. On the other hand, the role of opioids in the management of neuropathic pain has been controversial. Until recently, opioids were reexamined in relation to neuropathic pain and proved efficacy. This study evaluated the use of pregabalin as an adjuvant analgesic added on tramadol treatment compared to tramadol alone in management of neuropathic pain in pediatric cancer. Methods: In a prospective, randomized, single blinded, parallel treatments groups study, patients were randomized to either tramadol group (T group, n=17) or combined pregabalin and tramadol group (P/T group, n=17). Children were followed for 4 weeks. Paracetamol as rescue analgesic medication was allowed during the study period. Baseline intensity of pain (on a numeric rating scale, NRS from 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable) was recorded during the enrollment visit and then recorded by the parent on daily basis in a pain diary, where a median value for each week was determined. Touch-evoked pain on an affected skin area (tactile allodynia) was assessed. Total paracetamol daily rescue doses were recorded. Daily recordings were averaged every week. Incidence and intensity of side effects were also recorded. Results: Thirty two patients out of thirty four completed the study. There was a significant difference at the fourth week of study in the combined P/T group when compared to T group. Nevertheless, significant improvement occurred in both groups when compared to baseline median values. The degree of pain reduction in the combined P/T group in the 4th week of the study in comparison to baseline median values was significantly higher than that occurred in tramadol group (75% Vs 37% respectively). The mean total daily paracetamol consumption as rescue medication was significantly lower in combined T/P group than in T group. The incidence of side effects was relatively high, but more evident in combined P/T group. Tiredness, dry mouth and constipation were the most frequent adverse events in T group while dizziness tiredness, dry mouth and somnolence were the most frequent in P/T group. Conclusion: Pregabalin was an efficacious add-on adjuvant with tramadol in management of neuropathic pain in pediatric cancer patients. The absence of pharmacokinetic interactions makes it a good choice in pediatric cancer patients with multiple comorbidities and many supportive treatments. However, the possibility of additive effect of adverse events with combination of therapies was suggested yet combination remained to be tolerable.