# Inclence of Chronic Pain following Oral Soft Tissue Biopsies: A Retrospective Study
## 4 Discussion  
In this study, we aimed to evaluate the incidence of chronic, possibly neuropathic, pain following soft-tissue biopsies in the oral mucosa and to correlate it with the biopsy site and histopathological diagnosis. To best of our knowledge, this is the first study on the incidence of chronic pain following oral soft-tissue biopsies. The files of 695 patients who underwent an intra-oral soft tissue biopsy were examined retrospectively. Four patients developed chronic pain at the biopsy site with no correlation to location or histopathological results (Table 2). The prevalence of PPTTN development after other common procedures in the oral area has been studied extensively [8; 9; 10; 11], including local anesthesia in mandibular injections [12]. Interestingly, the chance of developing chronic pain after oral procedures with no bone involvement is relatively high. For example, PPTTN or sensory abnormalities after root canal therapy including pulp tissue removal occurs in 3-13% of cases [7; 13]. A systematic review and meta-analysis estimated the frequency of all-cause persistent tooth pain after endodontic procedures to be 5.3% [14]. Biopsy for pathological investigation is a routine procedure that obviously causes tissue injury/trauma. Wound healing is the process of restoration of tissue integrity after trauma and has four major phases: hemostasis, inflammation, proliferation, and tissue remodeling [15]. This process is faster and leaves less scarring in the oral cavity than the skin due to accelerated immune response, and higher extracellular matrix remodeling rate [15]. Previous studies evaluated acute pain during tissue healing following oral biopsy. [PERSON] et al., assessed immediate pain up to 7 days after biopsy and noted that only 0.03% of patients had pain for more than 3 days after the procedure [16]. [PERSON] et al. recorded maximum pain and swelling after oral mucosal biopsy during the first 48 h [17]. [PERSON] et al., assessed pain during three days after oral mucosal biopsy. A total of 40% of patients reported moderate pain on the day of the biopsy and 58% of patients did not have any pain at all on the third day after the biopsy. Moreover, there was no relationship between the average level of pain and the location of the biopsy, type of biopsy, type of coverage, maximum diameter and type of lesion [18]. This agrees with the results of the present study, where no correlation was found between pain, biopsy site or diagnosis. The rate of pain after skin biopsy is also not well defined and seems related to the size and location of the biopsy site, the depth of the biopsy, the technique used, and individual patient factors. However, various studies indicate that the Mohs procedure (for treating skin cancer, where individual layers of skin are removed and examined to determine if they are cancer-free) is comparable to oral soft tissue biopsy, because it is generally non-painful and well-tolerated by all genders across all ages [19; 20]. In our study, 4 patients out of 695 (0.575%), reported chronic pain at the biopsy site 3 months after the procedure (see Table 2 for pain and patient characteristics). All four were women, which is congruent with most other publications that describe a higher rate of post-operative pain in women, e.g., female gender was associated with more severe postoperative pain after root-canal treatment in a cohort of 270 patients [21], and after Mohs Micrographic Surgery [19]. Although we did not include a VAS pain score in the long-term follow-up of the four patients with PTTN, the fact that they did not need analgesics means that they were experiencing mild pain. It is important to note the considerable overlap between inflammatory and neuropathic pain processes, making it difficult to differentiate whether a particular chronic pain is nociceptive, inflammatory or neuropathic since all three mechanisms are involved in healing following trauma [22].