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Pain Trials as a Tool

Pain trials are a valuable tool to use in managing your chronic pain cases. In this Pain Update we review how we use pain trials, what we should consider alongside this and we make some recommendations.



An analgesic trial, or pain trial, involves the prescription of analgesic(s) where we are suspicious of pain. The response to this intervention is then monitored to determine if the clinical signs have resolved with analgesic treatment.


So where do we start?

Common questions are which analgesics to choose and how to monitor the response to those? We will review some commonly used analgesic options and discuss some tools to use to monitor progress.


We need outcome measures!

Diagnosis of chronic pain is often not easy and can be greatly assisted by an analgesic trial. Key to this is monitoring the response to treatment. This can be done in a variety of ways. A really simple option which I find valuable is asking the client to define some pain behaviours - these are changes in the pet's behaviour that the owner associates with pain.


These are also known as Client Specific Outcome Measures (CSOMs) or Client Reported Outcome Measures (CROMs) and their use deserves some focus here. During our history taking we can often identify these behaviours and work with the client so they understand that we are using these as outcome measures at our next consultation. I tend to identify 3-5 behaviours. I recommend reading further on this topic. The linked article here by Prof John Innes highlights why CROMs should become part of our routine.


The author suggests that the everyday use of CROMs would bring benefits to animals with chronic health conditions and improve the impact that our profession can have on animal welfare


In addition to these pain behaviours we can also use various metrology instruments - examples being the Canine Brief Pain Inventory (OA pain & cancer pain), Liverpool OA in dogs (OA), Feline Musculoskeletal Pain Index (FMPI). In this link you can see which pain scales are validated.


To me, a huge part of outcome measures is my physical exam. In that initial consultation we are documenting where the pain is. Of course the pain we detect is not always the primary source of pain and we may be identifying areas of secondary compensation for example muscular pain. At each and every visit we go back to basics and use that physical exam to support what the owner and the pain scores are telling us.


We now know what we are measuring, so what next?

Armed with the ability to measure the impact of our intervention, we need to provide some rationale around which analgesic to use.


Where is the pain coming from?

An understanding of pain aetiology can help us narrow down the pain type. We consider pain types as three broad categories, as per the IASP definitions.


Nociceptive/inflammatory

Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.

Note: This term is designed to contrast with neuropathic pain. The term is used to describe pain occurring with a normally functioning somatosensory nervous system to contrast with the abnormal function seen in neuropathic pain.

Analgesic choices include NSAIDs, grapiprant, anti-NGF products, opioids.


Neuropathic

Pain caused by a lesion or disease of the somatosensory nervous system.

Note: Neuropathic pain is a clinical description (and not a diagnosis) which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria.

Read our Pain Update here on neuropathic pain

Analgesic choices include gabapentin or pregabalin. Our webinar 'An in-depth look at gabapentinoids' will help you navigate the use of the gabapentinoids.


Nociplastic

Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.

Note: Patients can have a combination of nociceptive and nociplastic pain

Read this link for a review on nociplastic pain.


Nociplastic pain is poorly recognised in dogs and cats. If you are suspicious of nociplastic pain, then we would be happy to help via a telemedicine consultation.


Our webinar Chronic Pain: Plan B is designed to help your decision making in those patients where the pain progresses and further analgesia is required. Which analgesic is best in any given situation?


Do we need an imaging diagnosis?

Recent information teaches us that owners of dogs with OA are more likely to comply with treatment recommendations where a radiographic diagnosis has been achieved. The definition of neuropathic pain from IASP uses the term 'demonstrable lesion' which suggests we should pursue diagnostics. From a clinical perspective, it is of course far easier to treat effectively if we understand our diagnosis.



Starting a pain trial

With clear outcome measures defined and hopefully an understanding of pain type, we can choose an analgesic for our pain trial. As a very general rule, we should provide analgesia for a reasonable period of time before attempting to judge efficacy. There is limited evidence in this area and we make recommendations here, rather than hard and fast rules. Where possible we should use licensed options.


NSAIDs

This is the one area where we have firm evidence regarding onset and efficacy. We see an effect from NSAIDs within 7 days. In one study examining enflicoxib (Daxocox) in dogs with OA, pain scores continued to decrease from day 0 to day 42. You can read that study here.

Recommendation - prescribe for 30 days then reassess.


Anti-NGFs

Frunevetmab - in this study, there was an improvement in CSOMs with treatment at day 28, which increased at day 56.

Recommendation - ask cat owners to report CSOMs back to you at 7 day intervals


Bedinvetmab - in this study, significant improvements in CBPI scores were noted at day 28 in dogs treated with bedinvetmab.

Recommendation - owners often report a positive effect within 7 days.


Gabapentinoids (not licensed)

With initial prescription of gabapentin we often see sedation in gabapentin naive patients. There are few studies evaluating the analgesia associated with gabapentin, especially with chronic pain. I now recommend starting low (5mg/kg BID) and titrating up to 10mg/kg TID to avoid sedation. That process will take one month.

Recommendation - prescribe for 30 days then reassess.


Amantadine (memantine) (not licensed)

In the Lascelles et al study amantadine was administered in conjunction with meloxicam for three weeks, and then the dogs were reassessed. This doesn't mean amantadine takes 3 weeks to work, it simply reflects the fact that the assessment interval was 3 weeks.

The NMDA antagonists are chosen where central sensitisation is suspected. If a peripheral driver is responsible for central sensitisation (ie: OA) then analgesics directed at that peripheral driver should also be used (ie: NSAIDs, anti-NGF).

Recommendation - prescribe for at least 21 days then reassess.

(Note - recommendations for memantine follow those of amantadine - for more info click here)


Ketamine (not licensed for chronic pain)

The rationale for using ketamine is where we suspect central sensitisation. Central sensitisation can occur in all pain types and one source suggests using ketamine to evaluate whether the patient could be experiencing central sensitisation.

Our webinar on Subcutaneous Ketamine covers the literature and rationale for the use of ketamine in chronic pain.

Recommendation - trial ketamine in the individual as a single injection with a view to this lasting one month. Inform the client that they may see an effect within days and it could last one month.


Our chronic pain cases do present us with challenges. A pain trial can be rewarding and help us improve quality of life in our patients. Quality of life is a valid outcome measure which we can monitor using a tool such as Vetmetrica, in both dogs and cats.


Now, with an understanding of how to approach a pain trial you are better equipped to deal with chronic pain. If you need help with a challenging case, please feel free to use our telemedicine service for advice.


This post was written by Matt Gurney.


Matt & Carl established Zero Pain Philosophy to provide educational resources & telemedicine to veterinary professionals globally, enabling optimal management of pain.


Matt Gurney is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and works at Anderson Moores Veterinary Specialists. Matt is Past President of the European College of Veterinary Anaesthesia & Analgesia and works at Eastcott Referrals in the UK.


Carl Bradbrook is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and is Past President of the Association of Veterinary Anaesthetists. Carl works at Anderson Moores Veterinary Specialists in the UK.


The intended audience for this pain update is veterinary professionals. This pain update is based on clinical experience and independent opinion.


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