The NGF System and its interplay with endocannabinoid signalling, from peripheral sensory terminals to the brain: new targets for the development of next generation drugs for neuropathic pain

The PAINCAGE project supports the European Union initiatives to promote gender equality and the work of the European Parliament‘s Committee on Women’s Rights and Gender Equality.

The European Commission Policy has been considering with great attention gender issues, and in February 1999 the European Commission has adopted the Women and Science Action Plan. Since then, the gender issue in science has become an important part of European Research policies, supported both by the European Parliament and the national governments.

The PAINCAGE gender equality policy is based on at least two combined objectives:

  1. The Consortium Gender profile
  2. The Gender issue in the research topic

Consortium gender profile: It was widely recognized that a transition to a both gender-balanced and gender sensitive organisation is needed to promote gender integration into research where the total participation rate of women is particularly low. Women involved in the PAINCAGE project as key staff are close to 50% and 4 out of 9 Partner leaders are women. The Coordinator and the partners are aware of the Commission policies on gender issues dealing not only with science made by women, but also with science for and on women (EUCOM 76/1999).

The Coordinator will monitor the project to avoid discriminating actions, at the level of vacancies to be filled, paying attention to an equilibrated distribution at the different professional levels. Whenever necessary, positive actions will be implemented for part-time work in order to facilitate the participation of persons with family, or following maternity/paternity leaving. The state of art of the gender issue in the project will be integral part of the Annual Report. PAINCAGE is aligned to the guidelines issued by The European Gender Summit – more women in science, better research results for everybody (European Parliament, Bruxelles, November 2012). The Summit has launched the development of a European gender equality standard – a guideline for better research and innovation practices.

The PAINCAGE partners are committed to promote equal employment opportunities and to continue the programme of actions to make this policy fully effective. Few women scientists have access to leadership positions despite the fact that they represent half of the student population, they only hold 10% of the senior positions in academia and even less in industry. The objective is to maintain the participation rate of women throughout the project by implementing a specific action plan as a tool to encourage and awaken all partners to the gender issue, according to the European Commission Policy.

The plan reports actions to support the involvement of women in the European research activities, in management boards and in scientific committees. The main items of the mentioned Action Plan are:

  • To recruit female researchers at all levels of the project,
  • To form an internal network of female researchers in the project,
  • To create in the project web site a section dedicated to the promotion of gender equality within the project,
  • To establish a system for monitoring gender equality in mobility schemes such as equality of access and participation and subsequent impact on professional careers.
  • To involve in the project women associations with a scientific imprinting, as the Equality Challenge Unit Athena Swan “Women in Science” (
  • A set of gender indicators will be produced in order to measure progress towards gender equality in the key positions. The Helsinki Group on Women and Science considers that the gendering of indicators on human resources in science is to be tackled from a threefold perspective: the ‘top-down’ approach, the ‘bottom-up approach, and the gendering of the benchmarking exercise.
  • An annual report will allow measuring progress concerning gender equity.

Gender issue in the research topic: Literature supports that the mechanisms underlying chronic nociceptive processing differ as a function of gender. Based on this evidence, PAINCAGE Partners will analyze and discuss, by gender, all data obtained from animal models and human samples. It is a clinical reality that women make up the large majority of chronic pain patients, and there is now consensus from laboratory experiments that when differences are seen, women are more sensitive to pain than men. Although sex differences in sociocultural, psychological, and experiential factors likely play important roles, evidence largely from animal studies has revealed surprisingly robust and often qualitative sex differences at low levels of the neuraxis.

Although not yet able to affect clinical practice, the continued study of sex differences in pain may have important implications for the development of new analgesic strategies.

Another important aspect that will be taken into account in human studies concerns sex-related differences in pain perception as well as in responses to pharmacological treatments. Today it is well known that the differences between sexes include not only the occurrence of chronic pain but also the kind of pain syndromes experienced, the characteristics of the complications that develop (Greenspan et al, 2007). Epidemiological and psychophysical studies demonstrated higher prevalence of painful disorders (e.g. migraine, temporomandibular joint disorder, fibromyalgia, arthritis and interstitial cystitis, multiple sclerosis) as well as higher susceptibility to nociceptive stimuli and more frequent use of analgesic medications in women than in men. Evidence is growing that sex differences in pain are due by a convergence of multiple factors, from genes to hormonal and cultural influences. It has been shown that estrogen exerts direct effects on nociceptor neurons to promote axon outgrowth, and this occurs through an NGF-independent mechanism (Blacklock et al, 2005). Furthermore, gender issue seems to affect the role of NGF in modulation of inflammation. Identification of possible sex differences in the EC and NGF system in patients could have important impact on clinical applicability with considerable implications also for health economics.


On the spotlight / About Gender Issues…

Experimenter sex can affect apparent baseline responses in behavioral testing:  A recent publication, Robert E Sorge, Loren J Martin, Kelsey A Isbester, Susana G Sotocinal, Sarah Rosen, Alexander H Tuttle, Olfactory exposure to males, including men, causes stress and related analgesia in rodents, Nature Methods 11, 629–632 (2014), has revealed that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla.


Useful links

Equality Challenge Unit, Athena Swan

FEMM Committee on Women’s Rights and Gender Equality

EPWS European Platform of Women Scientist

AVIS Association for Women in Science

Gender Summit

Associazione Donne e Scienza