The project will assess the expression and receptor characteristics of neuropeptides representing nociceptive, antinociceptive, vasoactive and immunoregulatory functions in bone, joints and muscle under normal and pathological conditions.

The project design, synthesize, pharmacologically characterize and experimentally test, in laboratory animals, a new generation of opioid compounds which combine potent antinociceptive and anti-inflammatory effects in the periphery without he classical central side effects of opioid drugs.

The project consists of the following work packages:

WP 1: Neuropeptides – expression in musculoskeletal tissues under normal and
pathological conditions

WP 2: Opioid receptors- expression in musculoskeletal tissues under normal and
pathological conditions

WP 3: Cell surface markers and cytokines in lymphoid and synovial tissues under

normal and pathological conditions

WP 4: Delta-opioid receptor antagonists – design and synthesis

WP 5: Delta-opioid receptor agonists – design and synthesis

WP 6: Synthesis of quaternized and ionizable derivatives of 14-methoxymetopon

WP 7: Biological characterization of the opioid compounds

WP 8: Synthesis of large quantities of opioid compounds

WP 9: In vivo pharmacological characterization of the opioid compounds

WP 10: In vitro immunomodulatory effects of the opioid compounds

WP 11: Effects of opioids on the development of arthritis and the underlying