OCTOBRE 2018 - ACTUS DOULEURS

 
  1. Investigation of sensory thresholds in Cavalier King Charles
    Spaniels with and without Chiari‐like malformations and syringomyelia

  2. The pharmacokinetics of gabapentin in cats

  3. Acute Pain in Cats: Recent advances in clinical assessment

  4. Comparison of transdermal fentanyl and oral tramadol for post-operative
    analgesia in dogs undergoing lateral thoracotomy

  5. PIEZO2 mediates injury-induced tactile pain in mice and humans

  6. Substance P and pain chronicity

 

 

1/ Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari‐like malformations and syringomyelia

Courtney R. Sparks, Angela Gorney, Kim Williams, Emily H. Griffith, Sofia Cerda‐Gonzalez, B. Duncan X. Lascelles, Natasha J. Olby
J. Vet. Intern. Med., First published: 11 October 2018

Résumé

Cavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari‐like malformation and syringomyelia (CMSM).
People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS.

Objectives

To use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM).

Animals

Forty‐four CKCS.

Methods

Prospective study. Dogs underwent neurological examinations and craniocervical magnetic resonance imaging (MRI).

Thermal testing was performed over the humerus and thorax (n = 32); mechanical testing was performed on the paw and neck (n = 44).

Latencies, thresholds, and response rates were compared with presence and severity of SM on MRI, presence of pain reported by the owner and pain identified on examination.

Results

Thirty dogs had SM, 30 were painful on examination, 29 were owner‐reported symptomatic.
Thermal and mechanical variables were not significantly different based on presence or severity of SM.

Dogs with pain on examination had decreased mechanical thresholds on the paw (0.38 kg, SD = 0.18) and neck (2.05 kg, SD = 0.74) compared to thresholds of dogs without pain on examination on the paw (0.60 kg, SD = 0.30) and neck (2.72 kg, SD = 0.57; P = .021).

Conclusions and Clinical Importance

Mechanical and thermal sensitivity does not appear to be related to the presence of SM, but mechanical sensitivity appears to be related to the presence of pain and clinical signs.
Mechanical testing may be useful for assessing sensory abnormalities during clinical trials.

PDF à https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.15297


2/ The pharmacokinetics of gabapentin in cats

Derek Adrian, Mark G. Papich, Ronald Baynes, Emma Stafford, B. Duncan X. Lascelles J. Vet. Intern. Med., First published: 11 October 2018

Résumé

Gabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats.
Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking.

Objectives

To evaluate the pharmacokinetics of clinically relevant dosing regimens of gabapentin in cats.

Animals

Eight research‐purpose mixed‐breed cats.

Methods

Cats were enrolled in a serial order, non‐randomized pharmacokinetic study.
Gabapentin was administered as an IV bolus (5 mg/kg), orally (10 mg/kg) as a single dose or twice daily for 2 weeks, or as a transdermal gel (10 mg/kg) in serial order. Serial blood samples were collected up to 48 hours.
Plasma concentrations were determined using Ultra Performance Liquid Chromatography‐Mass Spectrometry.
Compartmental analysis was used to generate gabapentin time‐concentration models.

Results

After IV administration CL (median (range)) and terminal half‐life were 160.67 mL/kg*hr (119.63‐199.11) and 3.78 hours (3.12‐4.47), respectively.
The oral terminal half‐life was 3.63 hours (2.96‐4.77), and 3.72 hours (3.12‐4.51) for single and repeated dosing.
TMAX and CMAX, as predicted by the model were 1.05 hours (0.74‐2.11), and 12.42 μg/mL (8.31‐18.35) after single oral dosing, and 0.77 hours (0.58‐1.64), and 14.78 μg/mL (9.70‐18.41) after repeated oral dosing.
Bioavailability after a single oral dose was 94.77% (82.46‐122.83).

Importance

Repeated oral dosing of gabapentin did not alter the drug's pharmacokinetics, making dose adjustments unnecessary with long‐term treatment.
As prepared, the transdermal route is an inappropriate choice for drug administration.
These relevant data are important for future studies evaluating potential efficacy of the medication for treating chronic pain states in cats.

PDF à https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.15313


3/ Acute Pain in Cats: Recent advances in clinical assessment

Paulo V Steagall, Beatriz P Monteiro
J. Fel. Med. Surg., First Published October 15, 2018

Résumé

Pain assessment has gained much attention in recent years as a means of improving pain management and treatment standards.
It has become an elemental part of feline practice with ultimate benefit to feline health and welfare.
Currently pain assessment involves mostly the investigation of sensory-discriminative (intensity, location and duration) and affective-motivational (emotional) domains of pain.
Specific behaviors associated with acute pain have been identified and constitute the basis for its assessment in cats.

Recent advances

The publication of pain scales with reported validation - the UNESP-Botucatu multidimensional composite pain scale and the Glasgow feline composite measure pain scale -and species-specific studies have advanced our knowledge on the subject.
Facial expressions have also been shown to be different between painful and non-painful cats, and very recently the Feline Grimace Scale has been validated as a tool for acute pain assessment.

Clinical challenges

Despite recent advances, several challenges still exist.
For instance, the effects of disease and sedation on pain scoring/ assessment are unknown.
Also, specific painful conditions (eg, dental pain) have not been systematically investigated.
The development and validation of instruments for pain assessment by cat owners is warranted, as these tools are currently lacking.

Aims

This article reviews the use, advantages, disadvantages and limitations of the two validated pain scales, and presents a practical, stepwise approach to feline pain recognition and assessment using a dynamic and interactive process.
The authors also offer perspectives regarding current challenges and future directions.


4/ Comparison of transdermal fentanyl and oral tramadol for post-operative analgesia in dogs undergoing lateral thoracotomy

Kate Read, Mahmuda Kahtun, Helen Murphy. Vet. Anesth. Analg., In Press, Accepted Manuscript, Available online 13 October 2018

Résumé : 

To compare analgesic efficacy and suitability of an existing oral tramadol-based protocol with a transdermal fentanyl-based protocol following lateral thoracotomy in dogs. Study Design: Prospective randomised clinical trial. 

Animals

Sixteen healthy laboratory beagle dogs. 

Methods

Dogs were randomly allocated to one of two treatment groups:

  • Group F (intramuscular methadone 0.2 mg kg-1 and transdermal fentanyl 2.6 mg kg-1 both administered on discontinuation of anaesthesia, n = 8)

  • or Group T (intramuscular methadone 0.2 mg kg-1 on discontinuation of anaesthesia and again 4 hours later, followed by oral tramadol 12 mg kg-1 per 24 hours commencing 7 hours after discontinuation of anaesthesia, n = 8).

Intercostal bupivacaine (0.5-1 mg kg-1) and subcutaneous carprofen (4 mg kg-1) was administered to all dogs at induction.
Bodyweight (BW), presence of clinical signs, pain score, activity, heart rate (HR) and mean arterial pressure (MAP) were assessed for 72 hours postoperatively. 

Results

No significant differences were observed in BW change, presence of clinical signs or gross locomotor activity between groups.

Pain scores were low at all times for all dogs and rescue analgesia was not required.

Dogs in Group T exhibited higher pedometric activity (p=0.006), HR (p<0.001) and MAP (p<0.001) than those in Group F; particularly the first night following surgery.

Least squared mean (LSM) pedometric activity was 1.81 and 1.02 jerks minute-1, LSM HR was 111.13 and 78.64 beats minute-1, and LSM MAP was 111.62 and 105.24 mmHg respectively in Groups T and F. 

Conclusions

and clinical relevance Both regimes appear to provide adequate analgesia following lateral thoracotomy in dogs.

Ease of administration of transdermal fentanyl compared to oral tramadol is advantageous.

Reduced activity observed with the fentanyl regime was not associated with any adverse effects and may be desirable following some invasive surgeries.

However, while transdermal fentanyl remains currently unavailable in the European Union, the oral tramadol-based regime provides an acceptable alternative.


5/ PIEZO2 mediates injury-induced tactile pain in mice and humans

Marcin Szczot, Jaquette Liljencrantz, Nima Ghitani, Arnab Barik, Ruby Lam, James H. Thompson, Diana Bharucha-Goebel, Dimah Saade, Aaron Necaise, Sandra Donkervoort, A. Reghan Foley, Taylor Gordon, Laura Case, M. Catherine Bushnell, Carsten G. Bönnemann and Alexander T. Chesler
Science Translational Medicine, 2018: Vol. 10, Issue 462, eaat9892

Résumé

Tissue injury and inflammation markedly alter touch perception, making normally innocuous sensations become intensely painful.
Although this sensory distortion, known as tactile allodynia, is one of the most common types of pain, the mechanism by which gentle mechanical stimulation becomes unpleasant remains enigmatic.
The stretch-gated ion channel PIEZO2 has been shown to mediate light touch, vibration detection, and proprioception.

However, the role of this ion channel in nociception and pain has not been resolved.
Here, we examined the importance of Piezo2 in the cellular representation of mechanosensation using in vivo imaging in mice.

Piezo2-knockout neurons were completely insensitive to gentle dynamic touch but still responded robustly to noxious pinch.
During inflammation and after injury, Piezo2 remained essential for detection of gentle mechanical stimuli.
We hypothesized that loss of PIEZO2 might eliminate tactile allodynia in humans.

Our results show that individuals with loss-of-function mutations in PIEZO2 completely failed to develop sensitization and painful reactions to touch after skin inflammation.

These findings provide insight into the basis for tactile allodynia, identify the PIEZO2 mechanoreceptor as an essential mediator of touch under inflammatory conditions, and suggest that this ion channel might be targeted for treating tactile allodynia.

PDF à http://stm.sciencemag.org/content/10/462/eaat9892/tab-pdf


6/ Substance P and pain chronicity

Cell and Tissue Research, p. 1–15, First Online: 03 October 2018
W. Zieglgänsberger

Résumé

Substance P (SP) is a highly conserved member of the tachykinin peptide family that is widely expressed throughout the animal kingdom.

The numerous members of the tachykinin peptide family are involved in a multitude of neuronal signaling pathways, mediating sensations and emotional responses (Steinhoff et al. in Physiol Rev 94:265–301, 2014).

In contrast to receptors for classical transmitters, such as glutamate (Parsons et al. in Handb Exp Pharmacol 249–303, 2005), only a minority of neurons in certain brain areas express neurokinin receptors (NKRs) (Mantyh in J Clin Psychiatry 63:6–10, 2002).

SP is also expressed by a variety of non-neuronal cell types such as microglia, as well as immune cells (Mashaghi et al. in Cell Mol Life Sci 73:4249–4264, 2016).
SP is an 11-amino acid neuropeptide that preferentially activates the neurokinin-1 receptor (NK1R).
It transmits nociceptive signals via primary afferent fibers to spinal and brainstem second-order neurons (Cao et al. in Nature 392:390–394, 1998).

Compounds that inhibit SP’s action are being investigated as potential drugs to relieve pain.

More recently, SP and NKR have gained attention for their role in complex psychiatric processes.

It is a key goal in the field of pain research to understand mechanisms involved in the transition between acute pain and chronic pain.

The influence of emotional and cognitive inputs and feedbacks from different brain areas makes pain not only a perception but an experience (Zieglgänsberger et al. in CNS Spectr 10:298–308, 2005; Trenkwaldner et al. Sleep Med 31:78–85, 2017).

This review focuses on functional neuronal plasticity in spinal dorsal horn neurons as a major relay for nociceptive information.

PDF à https://link.springer.com/content/pdf/10.1007%2Fs00441-018-2922-y.pdf

 

Morgan Cahouet