**4. Headache pain pathway**

**3.2. Physiopathology of tension-type headaches**

**Figure 1.** The pathways of migraine [11].

144 Pain Relief - From Analgesics to Alternative Therapies

Even though migraine represents a major public health concern and is the leading cause of headache, tension-type headache should not be underestimated since it represents It is a well-known fact that cerebral tissue has no pain receptors, making it impossible to generate painful stimuli directly from the brain; most head and neck tissues such as bone, muscle, skin, and even blood vessels share a common innervation pattern where nociceptive C and A-delta fibers from the first root of the trigeminal nerve are involved as seen in **Figure 2**.

The aforementioned common innervation pattern may cause headache to arise from almost any head structure from muscles to meningeal membranes progressing to a chronic condition based on preexisting genetic, biochemical, and behavioral characteristics of each individual. Once the pain has become chronic, at least two molecular events have been identified as responsible (totally or partially) for pain upregulation: low serotonin levels and high nitric oxide, both of them upregulating pain pathways in at least two major headache groups: migraine and chronic tension-type cephalalgia [23]. Based on the above, positive strides can be made toward the development of new drugs intended not only to treat pain but also to prevent it [24] since the existence of both a common neurologic pain pathway as well as shared molecular features among major primary headache groups provides that possibility; moreover, it could be possible to treat different primary headache types with a single drug working on key, shared points of the pain pathway [25]; however, more extensive research as well as a deeper understanding of different pain pathway integration is needed to achieve such goals; primary headache treatments still focus on two main targets: pain control and crisis prevention.

**Figure 2.** Blood vessel innervation pattern and migraine associate pain pathways [22].
