**2. Cancer pain**

The diagnosis of cancer is typically traumatic and full of uncertainties, due to its prognostic implications and the need for demanding treatment regimens. The word "cancer" still remains synonymous of "pain" and "death". Therefore, both mental and physical pain, in all the aspects and intensity of their clinical expression, characterize every stage of the disease. [11]

Cancer can cause pain at any time during its course, with frequency and intensity of pain tending to increase in the advanced stages. Indeed, roughly 75–95% of patients with metastatic cancer will experience significant amounts of cancer-induced pain.

According to the International Association for the Study of Pain (IASP), pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain occurring to cancer patients is defined as "total pain" (or "global suffering"), since people with cancer tend to manifest a wide array of functional needs (at a psychological, social, spiritual and existential level) that ought to be recognized and addressed in their complexity.

Relief of pain should, therefore, be seen as part of a comprehensive strategy of care addressing physical, psychological, social, and spiritual aspects of suffering. Physical aspects of pain cannot be treated separately from psychological aspects, whereas patients' anxieties cannot be effectively addressed while patients are physically suffering.

Therefore, all various components of cancer pain should be addressed simultaneously.

Knowledge of the mechanisms of pain has improved considerably over the past few years. We now know that physical injuries, pain pathways, and the emotional processing of this infor‐ mation are connected with each other within the nervous system. Anxiety, fear, and insomnia are re-elaborated at the level of the limbic system and the cortex. As a result, the brain responds sending signals back to the spinal cord and, thus, modifies the pain input at spinal levels. The spinal cord sends further impulses back to the brain, establishing in this way a reinforcing loop. [12]

there appears to be a deficiency in the training of physicians and nurses. Both physicians and nurses indicated that "inability to properly assess the pain" and "inadequate knowledge about pain management" ranked among the most relevant barriers preventing a multidisciplinary

Despite the increasing availability of pain medications, pain continues to be deemed as

According to a recent population-based study, investigating cancer pain in eleven European countries and Israel, 56% of patients suffered from moderate to severe pain in the previous

A systematic review completed in 2007 showed that cancer pain is present in 64% of patients with metastatic, advanced disease, in 59% of subjects undergoing cancer-related therapies. Despite effective, curative treatment, a moderate-to-severe pain intensity being reported in

Pain is present in over 50% of cancer patients, reaching higher percentages in patients with cancer at specific sites, such as stomach, uterus, lung, prostate, cervico-facial district, biliary

The diagnosis of cancer is typically traumatic and full of uncertainties, due to its prognostic implications and the need for demanding treatment regimens. The word "cancer" still remains synonymous of "pain" and "death". Therefore, both mental and physical pain, in all the aspects

Cancer can cause pain at any time during its course, with frequency and intensity of pain tending to increase in the advanced stages. Indeed, roughly 75–95% of patients with metastatic

According to the International Association for the Study of Pain (IASP), pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain occurring to cancer patients is defined as "total pain" (or "global suffering"), since people with cancer tend to manifest a wide array of functional needs (at a psychological, social, spiritual and existential level) that ought to be

Relief of pain should, therefore, be seen as part of a comprehensive strategy of care addressing physical, psychological, social, and spiritual aspects of suffering. Physical aspects of pain cannot be treated separately from psychological aspects, whereas patients' anxieties cannot be

Knowledge of the mechanisms of pain has improved considerably over the past few years. We now know that physical injuries, pain pathways, and the emotional processing of this infor‐

Therefore, all various components of cancer pain should be addressed simultaneously.

and intensity of their clinical expression, characterize every stage of the disease. [11]

cancer will experience significant amounts of cancer-induced pain.

effectively addressed while patients are physically suffering.

recognized and addressed in their complexity.

months, and 69% reported pain-related difficulties hindering everyday activities. [9]

approach to pain treatment and adequate cancer pain management. [8]

moderate-to-severe in more than 50% of cancer patients.

tract, breast, colon, brain, pancreas, cervix, and ovary. [10]

more than one third of all cancer patients.

**2. Cancer pain**

62 Updates on Cancer Treatment

**Figure 1.** Factors affecting patient's perceptions of pain (adapted from Waycross RG, Lack SA, Therapeutics in terminal disease, London: Pitman, 1984) from : Principles of control of cancer pain BMJ 2006; 332

Pain is a subjective, heterogeneous experience, affected by patient's genetic background, anamnestic record, mood, expectations, and culture. Cancer pain can be classified according to a number of different features (i.e., etiology or physiopathology).

There is a wide array of potential causes resulting in pain in cancer patients. Indeed, the painful experience involves inflammatory, neuropathic, ischemic, and compression mechanisms occurring in multiple sites. [13]

This section highlights some of the most common causes of pain in cancer patients:


Bone metastases are another common responsible of cancer-related physical impairment. Such causes of cancer pain may lead to nociceptive (somatic and visceral), neuropathic, or mixed pain; they may occur in combination with acute or active disease, subacute disease, or chronic disease undergoing palliative care-as well as disease in complete remission with residual effects.

Other sources of pain may include pathologic or osteoporotic stress fractures, and osteonec‐ rosis (following steroids or Radiotherapy). Chemotherapy (CT) side effects may include mucositis, while Radiotherapy (RT) side effects may present as odontophagia, mucositis, or burns.

Lymphedema resulting from RT or surgical excision may result in painful swelling surround‐ ing the affected region or the extremities, eventually leading to painful cellulitis or skin ulceration. A painful scar or keloid may occur following wound healing, carrying an increased risk of wound-site neoplasms.

A controversial aspect related to iatrogenic pain is the phenomenon of hyperalgesia observed during chronic treatment with opioids; although the exact mechanism underlying this phenomenon is still unknown, it seems to be related to tolerance to opioid drugs administered chronically, repetitive stimulation of spinal NMDA receptors, dynorphin activity at the spinal level, specific abnormalities of central processes regulating the neural transmission to the nerve, and a possible action of cholecystokinin at the central nervous system level. [14]

## **3. Cancer pain: Pathogenetic classification**

Onset and assistance of pain during the clinical course of cancer may stem from direct mass effect, relationship between tumor and host, iatrogenic damage; from a physiopathological standpoint, cancer pain may be classified as follows: [15]


**• Neuropathic pain** due to tumor infiltration / compression of nerves, plexuses, or nerve roots, remote effects of malignant disease on peripheral nerves or side effects of pharmacological treatments. [16]

Cancer pain shares the same neurophysiologic pathways as non-cancer pain. Such nociceptive mechanisms involve activation of sensory afferents by persistent noxious stimuli, signal transduction, transmission, modulation, and, finally, pain perception. [17]
