## 4 Discussion  
The main results of the present study suggest that in patients with knee OA, MT implies a decrease in the neuronal excitability in the spinal cord by means of a reduction in the TS after the application of four treatment sessions. MT led to a significant knee pain reduction after the first session and after the fourth session, while significant changes in the CPM and in the TS assessment were detected after the fourth session. Our study found significant changes in pain intensity after first and fourth session treatments. [PERSON] et al. [25] in a recent study compared two manual therapy techniques showing improvement in the pain intensity parameter after the intervention; moreover, the improvements occurred in both groups without any differences between the techniques. In addition, [PERSON] et al. [38] compared the effects of MwM mobilization with sham mobilization, finding a statistically significant decrease in the NPRS value post-treatment in both groups. In the literature, few studies assess the changes in TS following the application of MT in patients with knee OA. In a recent study, [PERSON] et al. [34] performed four sessions in four weeks of MT combined with either biomedical education or pain neuroscience education, investigating the TS in patients with knee OA. They did not find any significant improvements on the TS parameters after four sessions of MT nor at one month of follow \begin{table}
\begin{tabular}{c c c c c} \hline \hline  & **Baseline** & **1 st Session** & **4 th Session** & **Cohen’s d** \\ \hline \multirow{2}{*}{Knee} & \multirow{2}{*}{5.7 \(\pm\) 2.9} & Pain intensity, NPRS & \multirow{2}{*}{4.0 \(\pm\) 2.6 *} & \multirow{2}{*}{0.6} \\  & & 4.2 \(\pm\) 3.03 * & & \\ \hline \multirow{3}{*}{Knee} & \multirow{3}{*}{3.2 \(\pm\) 1.2} & PPT (kg/cm\({}^{2}\)) & \multirow{3}{*}{3.7 \(\pm\) 1.6} & \multirow{3}{*}{0.4} \\  & & 3.6 \(\pm\) 1.3 & & 4.1 \(\pm\) 1.9 & \\ \hline \multirow{3}{*}{Knee} & \multirow{3}{*}{2.6 \(\pm\) 2.1} & Temporal Summation & \multirow{3}{*}{0.6 \(\pm\) 1.5 *} & \multirow{3}{*}{1.1} \\  & & 1.5 \(\pm\) 1.5 & & \\ \hline \multicolumn{5}{c}{Conditioned Pain Modulation} \\  & & 3.1 \(\pm\) 1.1 & 3.3 \(\pm\) 1.2 & 3.8 \(\pm\) 1.4 * & 0.6 \\ \hline \hline \end{tabular}  
* NPRS: Numeric pain rating scale; PPT: pressure pain threshold;
* Indicates statistical significance \(p\) \(<\) 0.05.  
\end{table} 
Table 2: Mean (SD) and mean difference within the group for numeric pain rating scale, temporal summation, pain modulation and pressure pain threshold at all study visits. up in any of the considered groups. Instead, in our study, significant decreases in TS were found after the fourth session compared to the baseline measurement. In the present study, no significant changes in the PPT were detected in the lateral epicondyle and locally at the level of the knee after the first and fourth MT session. This is in contrast with the study of [PERSON] et al. [39], which defined that MT could reverse hyperalgesia at a local and a distant site, therefore suggesting effects at a central level. Despite this, in a previous published study by [PERSON] et al. [16] the knee PPT significantly improved immediately after joint mobilization, suggesting that joint mobilization may aid in facilitating central inhibitory mechanisms. In contrast with our study, [PERSON] et al. [27] found that MT resulted in greater immediate improvement of the PPT at the painful site and at a distant site (shoulder) in knee OA patients. The effect on the pain modulatory system, especially relative to the TS, could be explained by the neurophysiological effects that MT has been shown to produce on the CNS [40]. The hypothesis that MT would improve the facilitatory nociception and endogenous pain modulation, causing a reduction in the maladaptive mechanisms observed in the pain neuromatrix in patients with knee OA, remains an issue of clinical interest [41; 42; 43].