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IT

is now indisputable that osteoarthritis (OA) is a major

public health issue. It is the most common form of

arthritis and accompanied by pain and stiffness,

symptoms that impair quality of everyday life. Age is the strongest

predictor of the development and progression of osteoarthritis. The

increasing number of older people and the changes in lifestyle

(increased obesity and lack of physical activity) throughout the

world mean that the burden on people and society will increase

dramatically.Worldwide estimates are that 9.6% of men and 18%

of women aged ≥60 years have symptomatic OA. Since chronic

pain is a hallmark of OA, this condition takes a devastating toll on

health, lives and healthcare costs. Despite major progress in the

last few decades, we still have much to learn about the etiology,

pathogenesis, and progression of this disease; its etiology is not

fully understood.

New results from the Pain Pathophysiology Lab in Krakow point

to an innovative strategy for the treatment of OA which may yield

satisfactory results. Although a leading approach in drug design

is the design of selective compounds, the compounds acting on

more than one biological component can be more efficient than

standard selective treatments. A recent study conducted by Pain

Pathophysiology Lab members in collaboration with scientists

from the Endocannabinoid Research Group at the Institute of

Biomolecular Chemistry (CNR, Pozzuoli NA), and researchers

from the Laboratory of Microtomography, Faculty of Computer

Science and Materials Science, University of Silesia, has shown

that drug therapy aimed at concomitant inhibition of enzymatic

activity of fatty acid amide hydrolase (FAAH), and at blockade of

the transient receptor potential vanilloid subfamily member 1

(TRPV1) receptor activity, can lead to better results than those

achieved so far with the use of selective, single acting drugs.

These findings were published in the May 2015 issue of

PAIN,

the official publication site of the International Association for

the Study of Pain.

Current osteoarthritis therapy

Despite the investment of significant resources by the

pharmaceutical industry to identify novel analgesic drugs,

chronic pain still represents a difficult treatment challenge in a

large sector of the population. The mainstay of medical pain

therapy remains drugs that have been around for decades, e.g.

nonsteroidal anti-inflammatory drugs (NSAID), or drugs that

have been around for perhaps centuries, such as opiates. Many

patients, however, find that over-the-counter NSAID medications

are ineffective for pain relief. Opiates are very powerful

painkillers, but their clinical use is limited by adverse effects.

Consequently, chronic pain is often undertreated and remains

an unsatisfied need.

New treatment options

Over the past few years, significant scientific progress has been

made in our understanding of the mechanisms that underlie

inflammatory and chronic pain. Preclinical research has identified

new factors and mechanisms that are involved in the

development and maintenance of chronic pain, many of which

represent potential therapeutic targets. A key discovery was the

molecular cloning of the vanilloid (capsaicin) receptor, TRPV1, a

polymodal nociceptor on primary sensory neurons. Targeting

TRPV1 represents a new strategy in pain relief. Evidence of the

relations between TRPV1 and cannabinoid receptors, particularly

CB

1

, is accumulating. Pharmacotherapy with the use of novel

compounds, especially those with multiple mechanisms of action,

has attracted scientists’ interests.

Time to treat: ‘multi-target’ compounds as an

original approach to new analgesics

Despite the claimed therapeutic potential of TRPV1 antagonists,

only a few candidates have progressed through clinical trials,

because of unpredicted secondary effects such as hyperthermia.

Similarly, regardless of the analgesic properties of selective FAAH

The Pain Pathophysiology Lab is in search of an effective, preventive strategy to

slow down osteoarthritis progression

Slowing the progression

130

I S S U E S E V E N

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L

www.horizon2020projects.com

P R O F I L E

S O C I E TA L C H A L L E N G E S : H E A L T H & W E L L B E I N G

X-ray microtomography–based three-dimensional visualisation of the

knee joint samples during the development of osteoarthritis pain in the

iodoacetate injected rats at days 0 (A

1

-C

1

) and 28 (A

2

-C

2

). Samples

are presented in an anterior–posterior view (A), left and right views (B),

and a vertical cross-sectional view (C)