I am not a physician but here's my take, based on limited info.

• Pregabalin may be worth trying and makes sense, dose-wise for children compared with Gabapentin.
• Baclofen?
• There is nothing wrong with opoiods.
• In my opinion, there is a fad right now of exaggerated efficacy of cannabinoids for just about any indication. CBD and THC appear to work either on different systems. Alternatively, CBD may actually be something of an CB antagonist, if I remember correctly.

Best of luck with this sad case. Cost-benefit decisions are a factor, of course, in terms of overall prognosis.

Hi Miky, Thanks for your answer.

The child is artificially fed (PEG). General conditions are satisfactory. Bowel movement once a day. She is on laxatives and anti-reflux, as she had several ab-ingestis episodes).

As an anti-epileptic, she is given by the neurologist Vigabatrin. Indeed Pregabalin may be worth trying.

Wouldnt Baclofen be contraindicated given the already altered muscular activity? She doesn't stand, walk, or rais her head without help.

I completely agree with you for the exaggerated efficacy of cannabinoids for just about any indication. Indeed We want to change it.

As for opioids, I agree that there is nothing wrong with them. However, some of them reduce the seizures' threshold. can you recommend any? (buprenorphine patch?)

Boaz Samolsky Dekel, thanks for your reply. What a difficult situation. I suppose the neurologist is using vigabatrin monotherapy under the consideration of the case falling generally under West syndrome, for which it seems like vigabatrin is the first line treatment (not sure why).

I was thinking of baclofen because it tends to have per-patient beneficial effects unrelated to its antispasmodic action, such as for neuralgia while having a low side effect profile. One can speculate that the pain is related to neuropathy-like effects owing to etiology of the receptor mutation, so baclofen or pregabalin may make sense, if only abstractly. Both have anticonvulsant effect, as well, especially pregabalin. You mentioned GERD, and baclofen does actually seems to be quite effective for this and by reducing gastric secretion. Some contraindication may exist with vigabatrin, though, and this is probably the consideration with any additional medicine with a potential depressant profile.

Anyway, opioids do seem to reduce seizure threshold, as you say. However, it's not clear to what degree or under what circumstances, as far as I know. Perhaps some opioids have a worse profile for seizures than others owing to delta or kappa occupancy, but I think dwelling on these details is probably of more academic rather than practical consideration - there are limited options, really. Problematic agents like Demerol aside.

I think the buprenorphine patch makes the most sense - no first pass metabolism may be especially relevant in term of polypharmacy here. Pain relief is a priority but I guess the parents need to understand the risks of opioids especially in hypotonia. It's very difficult to predict. Maybe pregabalin will be beneficial, in any case.

Miky Timothy, Thanks for your clarifications.

I am going to see the girl this week and will try some of your suggestions.

Boaz Samolsky Dekel, I wish you the best of luck in providing your patient with pain relief. I have tremendous respect for what you are trying to do here and the work you and your group are pursuing. When I saw your post, I anticipated that, as often occurs on ResearchGate, others would simply reply with posts of biomedical papers on the topic, discussing the case as an abstraction. You as a clinician need to make the kinds of decisions regarding your work that academic researchers almost never have to and I wish more scientists would be cognizant of clinical reality.

For example, I've posted a pathway (GABA-B, baclofen), that the GNB1 protein has a regulatory role in. This is really interesting and it is amazing how much we now know about molecular physiology. Nonetheless, it must be acknowledged that this information, while promising, won't be of much help the girl, at present. Moreover, over-speculation as to the underlying mechanisms may take attention away from practical cost-benefit decisions that any answer to your question would be based on. Research pharmacologists typically deal with such pathway diagrams, but rarely with an image of, for example, a 'floppy baby' (not shown).

Anyway, the system is so complex and interconnected, with many 'permutations' of of the potential mutations. Moreover, the pathology involved is, I think, as much the result of problems during development as anything related to the GNB1 system at present. These two phenomena do not necessarily overlap.

Unfortunately, clinicians have very few options to deal with the resulting issues patients have, never mind any 'treatment'. Even if we had some kind of transgenic method to resolve the mutation in the 3-year, the damage to the neural wiring has been done. Pharmacotherapy is necessarily a blunt instrument with many unknowns. But it's the best we have.

In my answers, I've tried to be aware of the these things and to to empathize with all the parties involved (including the patient), in terms of risks and benefits. Let's hope for the best result in a very difficult situation.

Aside from NSAID, give Paracetamol drip at 20mg/Kg every 6hours and Nalbuphine at 0.3mg/kg IV over 10-15minutes, then 0.25-0.5mg/kg q 6hrs PRN for severe pain.

Dear

just i refer that link with all the purpose about evaluation and strategies .

Evaluation with multiple Scales can give a better purpose with clinical observation

and after we can think about strategies

https://pediadol.org/la-douleur-de-lenfant-strategies-soignantes-de-prevention-et-de-prise-en-charge/#Evaluation

Best regards

Thinking about non drug strategies

laser acupuncture

https://www.music-care.com/douleur.html