OCT 2018 - Buprénorphine - Anesthésie locorégionale - Immunothérapie



1/ The analgesic effects of buprenorphine (Vetergesic or Simbadol) in combination with carprofen in dogs undergoing ovariohysterectomy: a randomized, blinded, clinical trial

Ryota Watanabe, Beatriz P. Monteiro, Marina C. Evangelista, Amélie Castonguay, Daniel Edge and Paulo V. Steagall

BMC Veterinary Research, 2018, 14:304, Published: 5 October 2018


Buprenorphine is a potent lipophilic opioid analgesic that is largely used in the multimodal treatment of acute pain.
Simbadol (buprenorphine hydrochloride) is the first and only FDA-approved high-concentration formulation of buprenorphine for use in cats.
The aim of this study was to evaluate the analgesic efficacy of carprofen in combination with one of two commercial formulations of buprenorphine (Simbadol and Vetergesic, 1.8 mg/mL and 0.3 mg/mL, respectively) in dogs undergoing ovariohysterectomy.

Twenty-four dogs were included in a randomized, prospective, controlled, clinical trial.
Patients were randomly divided into 2 groups as follows.
Dogs were premedicated with acepromazine (0.02 mg/kg) and either 0.02 mg/kg of Vetergesic or Simbadol intramuscularly (Vetergesic group – VG; Simbadol group – SG, respectively; n = 12/group).

General anesthesia was induced with propofol and maintained with isoflurane in 100% oxygen.
Carprofen (4.4 mg/kg SC) was administered after induction of anesthesia.
Heart rate, respiratory rate, blood pressure, pulse oximetry, pain scores using the Glasgow Composite Pain Scale Short Form (CMPS-SF), sedation scores using a dynamic interactive visual analogue scale and adverse events were evaluated before and after ovariohysterectomy by an observer who was unaware of treatment administration.

If CMPS-SF scores were ≥ 5/20, dogs were administered rescue analgesia (morphine 0.5 mg/kg IM).
Statistical analysis was performed using linear mixed models and Fisher’s exact test (p < 0.05).


Pain and sedation scores and physiological parameters were not significantly different between treatments.
Three dogs in VG (25%) and none in SG (0%) required rescue analgesia (p = 0.109).

Adverse effects (i.e. vomiting and melena) were observed in two dogs in SG and were thought to be related to stress and/or nonsteroidal anti-inflammatory drug toxicity.


The administration of buprenorphine with carprofen preoperatively provided adequate postoperative analgesia for the majority of dogs undergoing OVH without serious adverse events.
Prevalence of rescue analgesia was not significantly different between groups;

however, it could be clinically relevant and explained by a type II error (i.e. small sample size).

Future studies are necessary to determine if analgesic efficacy after Simbadol and Vetergesic is related to individual variability or pharmacokinetic differences.

PDF à https://bmcvetres.biomedcentral.com/track/pdf/10.1186/s12917-018-1628-4

2/ Effects of hyaluronidase on ropivacaine or bupivacaine regional anaesthesia of the canine pelvic limb

Travis R. Gray, Brighton T. Dzikiti, Gareth E. Zeiler

Vet. Anesth. Analg., In Press, Accepted Manuscript, Available online 28 September 2018



To determine the effect of hyaluronidase on time to onset and offset of anaesthesia in ropivacaine or bupivacaine femoral-ischiatic nerve blocks.

Study Design

Blinded randomised crossover trial.


Eight beagle dogs.


Each dog underwent four treatments separated into two blocks - initially, the ropivacaine treatment block: RS (ropivacaine 0.5% plus saline 0.9%); RH (ropivacaine 0.5% plus hyaluronidase 100 IU mL-1); followed three weeks later, by the bupivacaine treatment block: BS (bupivacaine 0.5% plus saline); BH (bupivacaine 0.5% plus hyaluronidase).

The local anaesthetics were administered at 0.1 mL kg-1 per site.
Hyaluronidase and saline were administered at 0.02 mL kg-1 per site.

Performance of femoral-ischiatic blocks was aided by a combined ultrasound-electrolocation technique.
The mechanical nociceptive threshold was measured, until offset or 360 minutes, using an algometer to ascertain baseline, onset and offset of anaesthesia.
Onset and offset of anaesthesia were defined as a 25% increase above and as a return to <25% above baseline nociceptive threshold readings, respectively.


The median (range) onset of anaesthesia for RS and RH was 21 (3-60) and 12 (3-21) minutes, respectively (p = 0.141).
The offset was 270 (90-360) and 180 (30-300) minutes for RS and RH, respectively (p = 0.361);
while the onset was 24 (3-60) and 9 (3-27) minutes (p = 0.394), and offset was 360 (240-360) and 330 (210-360) minutes for BS and BH, respectively (p = 0.456).


and clinical relevance Hyaluronidase had no effect on the onset and offset times of ropivacaine and bupivacaine femoral-ischiatic nerve blocks in dogs compared to saline.
The onset and offset times were highly variable in all treatments.

Clinically, the high variability of the onset and offset times of the regional anaesthesia of these local anaesthetic drugs mean that clinicians must monitor the animal’s response and, if required, provide additional analgesic drugs.

3/ Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and immunotherapies

Min Xu, David L H Bennett, Luis Antonio Querol, Long-Jun Wu, Sarosh R Irani, James C Watson, Sean J Pittock, Christopher J Klein

Neurol. Neurosurg. Psych., 02 Oct. 2018


The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important— in pain modulation.

The result of these interactions is central and peripheral sensitisation of nociceptive processing.
Additionally, new insights and the term ‘autoimmune pain’ have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability.

Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways.
Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4).

These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness.
Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response.

Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches.
Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed.

Thierry Poitte