EFIC Symposium: New therapeutic strategies to combat joint pain

Targeted therapy: Subgrouping people with arthritis pain

EFIC Topical Symposium 2016

Dubrovnik (ptp008/23.09.2016/09:50) Joint pain continues to be one of the main reasons for persisting disablement. One explanation, among others, is that pain therapies available today do not always have the desired effect. David Walsh, a professor from the University of Nottingham (UK), discussed new developments in this area at a symposium focusing on severe and chronic joint pain being staged in Dubrovnik by the European Pain Federation EFIC. "Researchers are currently investigating a number of interesting possibilities. The development of new drugs is an arduous process, however, we can most likely expect that NGF blockers, a completely new class of painkillers, will be available for therapeutic practice in the foreseeable future," Prof Walsh notes. NGF stands for "nerve growth factor".

In the meantime, many clinical studies have shown that blocking nerve growth factor can have a positive effect on arthritis pain, back pain and likely also other types of pain. A recent study (Xu L, 2016), in which Dr Walsh was involved, shows in the animal model, for instance, that treatment with the anti-NFG antibody muMab911 mitigates pain responses in connection with arthritis, doing so without preventing cartilage damage and synovitis. This study also indicates that indirect effects on subchondral bone remodelling could also contribute to the analgesic effect of the NGF blockade. Other drugs in development that prevent NGF signalling might equally reduce arthritis pain (Nwosu L, 2015, Ashraf S, 2016).

Targeted therapy

One research approach attempts to identify the mechanisms of pain and of pain transmission and then deactivate them - but only at the right places. Prof Walsh: "Without pain as a warning signal, people would be at constant risk of injury. That is why the experience of pain as a whole cannot be prevented." A team around Prof Walsh, Prof Wood and colleagues in London is identifying proteins that work as pressure sensors on nerves in the joint, and play an instrumental role in the arthritis pain when joints move or on standing.

Subgrouping people with arthritis pain

Prof Walsh: "To help people with joint pain more effectively, we need to recognise that not everyone is the same - for any one treatment people might either be responders for whom the analgesic works well or non-responders who might benefit more from other drugs." A lot of research is now underway to determine how patients can best be clustered according to type of pain and to the mechanism behind that pain.

"The advantage of this approach is this: You are able to offer the patient a targeted therapy that brings about important relief that outweighs any likely side-effects. I am firmly convinced that many of the drugs attested to be ineffective in the past might well have worked for some people, but those people were hidden in the clinical trials among the large group of persons for whom the drug didn't work, or whose pain even got worse. If we could identify the group of people for whom a treatment will work, new effective treatment possibilities could be found for them quickly," Prof Walsh emphasises.

Reliable treatments, new possibilities for using them

Prof Walsh sees another future field of investigation in the identification of therapies from other indication areas whose analgesic benefits were heretofore unknown or not sufficiently known. For example, arthritis typically involves nociceptive pain triggered by mechanical stimuli. If common analgesics do not work, drugs for combatting neuropathic pain can help in many cases - quite unexpectedly.

Other examples might be beta blockers, which have been prescribed for decades to combat high blood pressure. In the meantime, there is growing evidence that they can also affect the transmission of pain in certain people. Non-drug treatment approaches should also be revisited and tested. Prof Walsh: "In some circumstances, physical exercise or psychological interventions can be employed differently than before and efficiently for specific groups of people with arthritis pain. Here, too, we must filter out those patients who can benefit from certain psychological techniques or defined exercise programs."

For instance, patients who will continue to suffer severe pain after receiving a knee joint replacement can be predicted to a certain degree. Untreated depression is one of the predictors for postoperative problems. One reason, among others, may be that in some people the brain mechanisms active in connection with depression overlap with those that process pain. Prof Walsh: "It is therefore worthwhile looking into the question of whether antidepressants and cognitive behavioural therapy might also improve outcomes for some people needing joint surgery."

EFIC has declared 2016 to be the European Year against Joint Pain. The goal of this information campaign is to focus on a health problem from which more than half of the worldwide population over age 50 suffers. Against this background, experts attending the symposium in Dubrovnik are discussing the many current trends for understanding and treating joint pain.

Sources: Xu L et al: The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain, Osteoarthritis Cartilage. 2016 Sep;24(9):1587-95. doi: 10.1016/j.joca.2016.05.015. Epub 2016 May 18; Ashraf, S, Bouhana, KS, Pheneger, J, Andrews, SW, Walsh, DA. Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of inflammatory arthritis. Arthritis Res. Ther. (in press, April 2016); Nwosu, L, Mapp, PI, Chapman, V, Walsh, DA. Blocking the Tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis. Ann. Rheum. Dis. (in press). DOI-2014-207203.

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