A pilot feasibility study of gabapentin for managing pain in children with dystonic cerebral palsy

Background Gabapentin is often used to manage pain in children with dystonic cerebral palsy, however the evidence for its effectiveness in this population is limited. The primary objective of this feasibility pilot study was to assess the factors which might impact on a future randomised controlled trial including the ability to recruit and retain participants, assess adherence/compliance to the prescribed intervention, and ability to complete all outcome assessments. The secondary objective was to gather preliminary evidence for the effectiveness of gabapentin at reducing pain, improving comfort and reducing dystonia in children with dystonic cerebral palsy. Methods This open label pilot study recruited children aged 5–18 years with dystonic cerebral palsy and accompanying pain affecting daily activities from four centres around Australia. Children were prescribed gabapentin for 12 weeks and were assessed at baseline, 6 weeks and 12 weeks. The primary outcome was feasibility of the protocol. Secondary outcomes were pain behaviour, pain intensity, care and comfort, individualised goal setting and dystonia severity. Results Thirteen children (mean age 10.4 years (SD 2.4yrs), 9 females) were recruited from 71 screened over 15 months. Two children withdrew while eight children experienced side effects. There were issues with adherence to medication dosage regimens and data collection. Improvements were seen in pain behaviour, comfort and pain related goals at 12 weeks. Dystonia was not significantly changed. Conclusions Whilst gabapentin has potential to improve pain and comfort in children with dystonic CP, the feasibility of implementing a definitive randomised controlled trial is low. Alternative trials designs are required to further examine the effectiveness of gabapentin in this heterogeneous population. Trial registration The trial was registered with the Australian Clinical Trial Registry (ACTRN12616000366459) on 22/03/2016 and the Therapeutic Goods Administration (CT-2016-CTN-00500-1) on 22/06/2016.

Widespread nociceptive maps in the human neonatal somatosensory cortex

Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Signal to noise ratio and overall activation area did not differ with stimulus modality. Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin (HbO), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour.

Effects of holothuria extract on pain behaviour and Fos like immunoreactivity (FLI) in formalin pain

Introduction: The aim of this study was to determine the effects of gamat extract on pain behaviour and Fos like immunoreactivity (FLI) expression in the ventral posterolateral thalamus using the acute pain model. Materials & Methods: Fourteen Sprague-Dawley male rats (220-300 gram) were given intraplantar injection of 0.05ml formalin (1%) followed by intraperitoneal administration of either 4 mg/kg gamat extracts (Holothuria spp.) or saline (control). Behavioural changes were observed and rats were sacrificed 2 hours post-formalin injection. Immunohistochemistry testing was done on the brain sections. FLI was examined using a light microscope attached to an image analyser. The behaviour and FLI data were analysed using repeated measure analysis of variance and independent t-test respectively. Significance level was taken as p<0.05. Results: The control group has significantly higher pain scores compared to holothuria group (F (1) =13.635, p=0.003). There was significant reduction in the pain behaviour score in the holothuria group when compared to the control group in phase 1 (t (14) =2.9, p=0.012) and most of the time from 15 to 60 minutes post-formalin injection (t (12) =3.535, p=0.004). There was a significant reduction (P<0.05) in the number of FLI on the contralateral aspect of the ventral posterolateral thalamic nucleus in the group that received 4mg/kg of holothuria extract (63 3.18) compared to control group (84 6.36). Conclusion: This study showed that administration of holothuria extract significantly suppressed the pain behaviour and reduced the number of FLI in formalin injected rats compared to control.