**2. Ethiopathology**

The underlying mechanisms creating the pain are not clear, though it has been proposed that it is probably multi-etiological. The most accepted hypotheses are increased expression of the neuropeptide substance P (SP), underlying psychiatric disorders, nutritional deficiencies, and perifollicular inflammation [1, 2, 5–7]. Substance P is involved in pain perception by the nerve endings, and changes in the production and activity of substance P around the hair follicles may be responsible for the pain and burning sensation [8]. Hair follicles are innervated by unmyelinated neural plexuses located around the hair follicle stem cells. These nerve fibers contain neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP). These neuropeptides play an important role in the regulation of hair growth and are associated with the neurogenic inflammatory response. Perifollicular SP is also involved in the regulation of hair growth [9]. An imbalance in the tonic release of neuropeptides may result in inhibition of hair growth. Cutrer et al. hypothesized that chronic activation of the c-fibers, in addition to mediating inflammatory pain and follicular injury, might reduce SP and CGRP concentrations resulting in altered peribulbar antigen presentation and inhibition of further hair growth [10].

Another explanation may be an underlying psychiatric disorder. It has been found that 76% of the people who had trichodynia had psychopathic signs versus 20% in the control group, supporting this idea. Researchers have observed and speculated that there is a connection between psychopathologic findings (such as anxiety) and trichodynia [1, 5, 6, 11–14]. In 2006 Gupta and Gupta. found that numbness and pain are common symptoms of somatoform dissociation or conversion reaction [15]. Kivanç et al. found that trichodynia was associated with depression in the telogen alopecia group and with obsessive-compulsive personality disorder in the androgenic alopecia group [16]. However, this idea is controversial. Although increased rates of psychiatric problems have been reported in patients with trichodynia, Ozturk et al. found no association between trichodynia and depression or anxiety [17]. In this study the patients with telogen alopecia were consisting the control group, and they could have the opportunity to evaluate only the trichodynia patients.

Neuropathic pain can also be associated with nutritional deficiencies (Fe, B12, ferritin, zinc, vitamin D, vitamin E). Nutritional factors affect the hair directly, and dietary supplements containing B complex vitamins can influence hair growth [17–19]. Nutritional deficiencies have been reported in other cutaneous dysesthesia syndromes. For example, glossodynia is characterized by a burning sensation of the tongue and oral mucosa. Menopause, psychogenic disorders, and nutritional factors have also been suggested to cause this phenomenon [13]. However, evidence level is very low to confirm this nutritional hypothesis for trichodynia patients [20].
